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Elastic properties of various poly(hydroxybutyrate) (PHB) molecular conformations were examined using molecular mechanics calculations. Force-distance functions and Young's moduli were computed by stretching PHB molecules. Unwinding the helical conformation is initially characterized by a Young's modulus of 1.8 GPa. At higher strains, the helix transforms into a highly extended twisted form. In contrast to paraffins, planar PHB is bent, attaining maximum length in straightened but twisted conformations. Single-chain moduli depend on chain extension. Computed data were used to analyze elastic response of tie molecules in the interlamellar region of semi-crystalline PHB and how their
This chapter discusses the transmembrane transport of ions and small molecules across cell membranes. Ions and molecules must cross the membrane to enter or exit the cell, which they do through transport proteins embedded in the membrane. The chapter will cover the different types of transport proteins and mechanisms that facilitate the movement of these substances across the membrane.
This chapter discusses how proteins are transported into membranes and organelles within cells. Proteins destined for these locations have targeting sequences that are recognized by translocation machinery. The targeting sequences direct proteins to the correct membrane or organelle, where they are integrated or transported across the barrier.
A Multiset Rule Based Petri net Algorithm for the Synthesis and Secretary Pat...ijsc
Membrane computing is a branch of Natural computing aiming to abstract computing models from the structure and functioning of the living cell. A comprehensive introduction to membrane computing is meant to offer both computer scientists and non-computer scientists an up-to date overview of the field. In this paper, we consider a uniform way of treating objects and rules in P Systems with the help of Multiset rewriting rules. Here the synthesis and secretary pathway of glycoprotein in epithelial cells of small intestine is considered as an example. A natural and finite link is explored between Petri nets and membrane Computing. A Petri net (PN) algorithm combined with P Systems is implemented for the synthesis and secretary pathway of Glycoprotein. To capture the compartmentalization of P Systems, the Petri net is extended with localities and to show how to adopt the notion of a Petri net process accordingly. The algorithm uses symbolic representations of multisets of rules to efficiently generate all the regions associated with the membrane. In essence, this algorithm is built from transport route sharing a set of places modeling the availability of system resources. The algorithm when simulated shows a significant pathway of safe Petri nets.
A Multiset Rule Based Petri net Algorithm for the Synthesis and Secretary Pat...ijsc
Membrane computing is a branch of Natural computing aiming to abstract computing models from the structure and functioning of the living cell. A comprehensive introduction to membrane computing is meant to offer both computer scientists and non-computer scientists an up-to date overview of the field. In
this paper, we consider a uniform way of treating objects and rules in P Systems with the help of Multiset rewriting rules. Here the synthesis and secretary pathway of glycoprotein in epithelial cells of small intestine is considered as an example. A natural and finite link is explored between Petri nets and membrane Computing. A Petri net (PN) algorithm combined with P Systems is implemented for the synthesis and secretary pathway of Glycoprotein. To capture the compartmentalization of P Systems, the Petri net is extended with localities and to show how to adopt the notion of a Petri net process accordingly.
The algorithm uses symbolic representations of multisets of rules to efficiently generate all the regions associated with the membrane. In essence, this algorithm is built from transport route sharing a set of places modeling the availability of system resources. The algorithm when simulated shows a significant
pathway of safe Petri nets.
This document summarizes a research article that analyzes the unfolding molecular dynamics simulations of cyclophilin using surface contact networks and associated metrics. The researchers define network metrics to track changes in the hydrophobic core during unfolding. They examine if unfolding involves a dry molten globule state with unlocked side chains but no water penetration. The metrics are applied to distinguish dry/wet molten globules and transition states. Key residues involved in unfolding events are identified.
This laboratory project report details the expression and purification of the Clocl_2077 protein from Clostridium clariflavum for the purposes of crystallization and structural determination. The Clocl_2077 protein is a putative fused anti-sigma factor and sigma factor protein that may be involved in cellulose degradation regulation. The project involved cloning the Clocl_2077 gene, expressing it in E. coli, and purifying the protein using nickel affinity and size exclusion chromatography. Additional experiments were conducted to express and purify the CBM3b domain of the Clocl_1053 protein to test its ability to bind carbohydrates. The successful purification of Clocl_2077 paved the way for future crystallization
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This chapter discusses the transmembrane transport of ions and small molecules across cell membranes. Ions and molecules must cross the membrane to enter or exit the cell, which they do through transport proteins embedded in the membrane. The chapter will cover the different types of transport proteins and mechanisms that facilitate the movement of these substances across the membrane.
This chapter discusses how proteins are transported into membranes and organelles within cells. Proteins destined for these locations have targeting sequences that are recognized by translocation machinery. The targeting sequences direct proteins to the correct membrane or organelle, where they are integrated or transported across the barrier.
A Multiset Rule Based Petri net Algorithm for the Synthesis and Secretary Pat...ijsc
Membrane computing is a branch of Natural computing aiming to abstract computing models from the structure and functioning of the living cell. A comprehensive introduction to membrane computing is meant to offer both computer scientists and non-computer scientists an up-to date overview of the field. In this paper, we consider a uniform way of treating objects and rules in P Systems with the help of Multiset rewriting rules. Here the synthesis and secretary pathway of glycoprotein in epithelial cells of small intestine is considered as an example. A natural and finite link is explored between Petri nets and membrane Computing. A Petri net (PN) algorithm combined with P Systems is implemented for the synthesis and secretary pathway of Glycoprotein. To capture the compartmentalization of P Systems, the Petri net is extended with localities and to show how to adopt the notion of a Petri net process accordingly. The algorithm uses symbolic representations of multisets of rules to efficiently generate all the regions associated with the membrane. In essence, this algorithm is built from transport route sharing a set of places modeling the availability of system resources. The algorithm when simulated shows a significant pathway of safe Petri nets.
A Multiset Rule Based Petri net Algorithm for the Synthesis and Secretary Pat...ijsc
Membrane computing is a branch of Natural computing aiming to abstract computing models from the structure and functioning of the living cell. A comprehensive introduction to membrane computing is meant to offer both computer scientists and non-computer scientists an up-to date overview of the field. In
this paper, we consider a uniform way of treating objects and rules in P Systems with the help of Multiset rewriting rules. Here the synthesis and secretary pathway of glycoprotein in epithelial cells of small intestine is considered as an example. A natural and finite link is explored between Petri nets and membrane Computing. A Petri net (PN) algorithm combined with P Systems is implemented for the synthesis and secretary pathway of Glycoprotein. To capture the compartmentalization of P Systems, the Petri net is extended with localities and to show how to adopt the notion of a Petri net process accordingly.
The algorithm uses symbolic representations of multisets of rules to efficiently generate all the regions associated with the membrane. In essence, this algorithm is built from transport route sharing a set of places modeling the availability of system resources. The algorithm when simulated shows a significant
pathway of safe Petri nets.
This document summarizes a study that used simulations and calculations to investigate a brownian ratchet model of the myosin V motor protein. The study modeled the two head regions of myosin V as spheres attached by a string that can move along an actin filament. The head-actin interaction was modeled as an asymmetric saw-tooth potential representing the electrostatic interaction. Binding of ATP to the heads cancels the potential, allowing diffusion, while hydrolysis of ATP restores the potential and biases motion in one direction. Simulations of this brownian ratchet model and the myosin V system were performed and analyzed to understand how these molecular motors harness thermal fluctuations.
Here are the key changes that occur inside cells as a result of alterations in the amount of calcium in the cytoplasm:
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Several approaches are proposed to solve global numerical optimization problems. Most of researchers have experimented the robustness of their algorithms by generating the result based on minimization aspect. In this paper, we focus on maximization problems by using several hybrid chemical reaction optimization algorithms including orthogonal chemical reaction optimization (OCRO), hybrid algorithm based on particle swarm and chemical reaction optimization (HP-CRO), real-coded chemical reaction optimization (RCCRO) and hybrid mutation chemical reaction optimization algorithm (MCRO), which showed success in minimization. The aim of this paper is to demonstrate that the approaches inspired by chemical reaction optimization are not only limited to minimization, but also are suitable for maximization. Moreover, experiment comparison related to other maximization algorithms is presented and discussed.
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This study investigated secondary modifications of red blood cell membranes in patients with hereditary spherocytosis (HS), which is characterized by irregularly shaped and short-lived red blood cells. The researchers found evidence that HS red blood cell membranes experience increased oxidation in vivo and alterations in lipid raft proteins compared to healthy individuals. Identifying these molecular changes provides insights into the pathogenesis and clinical diversity seen in HS.
Chapter 4 A Tour of the CellChapter 4 A Tour of the CellName.docxwalterl4
Chapter 4: A Tour of the Cell
Chapter 4: A Tour of the Cell
Name ________________________ Period _________
Chapter 4: A Tour of the Cell
Guided Reading Activities
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1. The ____________ states that all cells come from existing cells and that organisms are made of cells.
2. Complete the table that compares prokaryotic to eukaryotic cells.
Prokaryotes
Eukaryotes
Description of cells
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B) Animal cell
C) Plant cell
D) Eukaryote
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Plant cells
Animal cells
Shared features
Unique features
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Complete the following questions as you read the fourth chapter content—Membrane Structure:
1. True or false: If false, please make it a correct statement. The plasma membrane regulates the movement of substances into and out of the cell.
2. Students, when asked to diagram a simple cell membrane, many times draw the structure
below. What is wrong with this structure? In other words, briefly explain why it is incorrect.
3. Which of the following statements best describes the structure of a cell membrane?
A) Proteins sandwiched between two layers of phospholipids
B) Proteins embedded in two layers of phospholipids
C) A layer of protein coating a layer of phospholipids
D) Phospholipids sandwiched between two layers of protein
4. A cell’s plasma membrane is described as being a ______________ because it is composed of a variety of molecules that are constantly in motion around each other.
5. Figure 4.5b on page 60 of your textbook indicates that membrane proteins will have both hydrophilic and hydrophobic regions. Briefly explain why a membrane protein would need both regions. Refer to the figure to aid you in answering the question.
7. List three common bacterial targets of antibiotics.
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1. Complete the following table regarding the nucleus.
Nuclear envelope
Nuclear pores
Nucleolus
Nucleus
Function
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A) Free-floating ribosomes
B) The nucleus
C) Ribosomes bound to the endoplasmic reticulum
D) Nuclear pores
3. What are the functions of a protein.
4. Does DNA lea.
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Similar to A Boolean Logic Cell Model of Vesicular Trafficking (20)
Chapter 4 A Tour of the CellChapter 4 A Tour of the CellName.docx
A Boolean Logic Cell Model of Vesicular Trafficking
1. A Boolean Logic Cell Model of
Vesicular Trafficking
Ashish Baghudana
National Center for Biological Sciences, Bangalore
Guided by:
Dr. Mukund Thattai
Simon Center for the Study of Living Machines
1
3. Abstract
Eukaryotic cells contain multiple membrane-bound organelles or
compartments. These compartments contain many proteins, which
are frequently exchanged with other compartments through packets
called vesicles. This process of exchange of molecules is called vesic-
ular trafficking. Each compartment and vesicle is identified uniquely
by its composition. Here, we represent each compartment and vesicle
by a Boolean string and describe the dynamics of vesicular transport
through functions on these Boolean strings.
Vesicular transport is a very specific process and is mediated through
several sets of proteins – SNAREs and Coat Proteins. These not only
dictate the specificity of transport, but also assist in the budding and
fusion of vesicles. These proteins can either be activators or inhibitors
of the fusion process. In this model, we abstract away the properties
of each protein and represent them as Boolean variables, which are
then used in molecular rules. These molecular rules describe which
vesicles can fuse with and bud from a compartment.
We have studied properties of these molecular rules by studying
their cognate Boolean formulae. We observed the satisfiability count
of these formulae to changes in the number of activators, deletion
and/or duplication of certain proteins and finally hybridization of sets
of molecular rules.
We find that fusion molecular rules obey a strict Disjunctive Nor-
mal Form. Subsequently, the satisfiability count of these formulae
depends on the total number of variables, the number of clauses and
the number of terms per clause in the formula. The set of budding
rules however, are more complicated and cannot be as easily repre-
sented as the fusion formulae.
1
4. 1 Introduction to the Mechanisms of Vesicle
Budding and Fusion
Newly synthesized proteins pass through a large number of membrane-bound
organelles or compartments on their way to the extracellular space, plasma
membrane, lysosomes, endosomes and so on. The main intermediate com-
partments in this transport chain are endoplasmic reticulum (ER) and the
Golgi apparatus. The Vesicular Transport Hypothesis established that such
secretory proteins are carried in vesicles[4]
. These vesicles “bud” from com-
partments in a process that selectively picks only some proteins to be part
of the vesicle. This selective incorporation is called “protein sorting”. These
vesicles are now targeted to other compartments that recognize the vesicle
and unload its contents into themselves[1] [4] [8]
. This process of budding and
fusion continues till the cell reaches a dynamic equilibrium where no new
proteins are being synthesized and the existing ones have reached their final
destination. Broadly, the mechanism of vesicle transport can be classified
into the following steps:
1. Protein Sorting
2. Vesicle Budding
3. Vesicle Tethering
4. Vesicle Fusion
1.1 Protein Sorting
Each vesicle contains a coat protein on the cytosolic surface. Three types of
coat proteins are known as of now: (a) Clathrin coat (b) COPII and (c)
COPI. These coat proteins are involved in both protein sorting and vesicle
budding[6]
. Coat subunit proteins polymerize at the vesicle-cytosol interface
and ultimately help the vesicle to pinch off from the compartment. Each coat
protein has two interfaces — adaptor side and cage side. The adaptor side
of the coat protein helps choose molecules from amongst the compartment
2
5. that form the cargo. Choosing occurs on the basis of protein sorting signals
in the form of motifs or 3-D structures of the protein. Protein sorting signals
are quite diverse and can consists of multiple motifs[5] [6]
.
1.2 Vesicle Budding
In addition to cargo selection, coat proteins are responsible for the change
in shape of the membrane. The cage side helps stabilize the vesicle bud-
ding process. The coat protein destabilizes the membrane and causes it to
deform. Some proteins in the coat protein complex also help stabilize the
curvature required for vesicle budding. The vesicle budding process is energy-
dependent. Therefore, each of these coat proteins are usually associated with
some GTPase activity that allows vesicle formation.[4]
Figure 1: Vesicle-dependent transport consists of 4 steps: Cargo Selection and Vesicle Move-
ment, Vesicle Budding, Vesicle Tethering and Vesicle Fusion. Sourced from Cai et. al., 2007[6]
3
6. 1.3 Vesicle Tethering
Vesicle tethering refers to the initial interaction between the vesicle and its
target compartment. Vesicle tethering is an important step in transport
as it brings the vesicle and its cognate compartment in proximity. Even if
a vesicle can fuse with a compartment, if tethers do not bring these two in
proximity, fusion does not occur. Together with RABs, small GTPases of the
Ras superfamily, tethers play an important role in determing the specifity of
vesicle targeting.
1.4 Vesicle Fusion
The final step in vesicular transport is the fusion of a vesicle with its target
compartment after they have been brought into close proximity. Fusion is
regulated by SNARE proteins .SNARE proteins are particularly well studied
and are related to three different neuronal proteins: synaptobrevin, syntaxin
and SNAP-25. These are sub-classified into V-SNAREs and T-SNAREs.
A V-SNARE on a transport vesicle pairs with its cognate T-SNARE on a
compartment followed by fusion[7]
.
4
7. 2 A Primer to Boolean Algebra
Boolean algebra is the field of mathematics which deals variables that can
have only two possible values: True or False. Boolean expressions use such
variables along with the following operators: Conjuction ∧, Disjuction ∨,
Negation ¬, Implication ⇒ and bi-Implication ⇔. Formally, these variables
are called Propositional Letters and Boolean expressions are known as Propo-
sitional Logic[2]
.
2.1 Basics of Boolean Logic
Boolean expressions are generated from the following grammar.
t ::= x | 0 | 1 | ¬t | t ∧ t | t ∨ t | t ⇒ t | t ⇔ t
where x ranges over a set of Boolean variables. As with algebra, Boolean
operators also have an order of precedence. The priorities, with the highest
first: ¬, ∧, ∨, ⇔, ⇒.
Any Boolean expression can be represented using a truth table. Using
the rules of precedence and truth tables given in Table 1, we can decide the
value of any Boolean function.
¬
0 1
1 0
(a)
∧ 0 1
0 0 0
1 0 0
(b)
∨ 0 1
0 0 1
1 1 1
(c)
⇒ 0 1
0 1 1
1 0 1
(d)
⇔ 0 1
0 1 0
1 0 1
(e)
Table 1: Truth tables for (a) Negation (b) Conjunction (c) Disjunction (d) Implication and (e)
Bi-Implication
A few other definitions that we use during this report are satisfiability
and satisfiability count. A Boolean formula is satisfiable if there exists at
least one assignment of variables such that the formula evaluates to True. If
a Boolean formula evalues to True for every possible assignment, it is called
5
8. a tautology. The satisfiability count of a Boolean formula is the number
of assignments of variables that evaluate to True.
2.2 Normal Forms of Boolean Expressions
A Boolean expression is in Disjunctive Normal Form (DNF) if it consists of
a disjunction of conjunctions of variables and their negations, also known as
a sum of products[3]
. It is of the form
(t1
1 ∧ t1
2 ∧ · · · ∧ t1
k1
) ∨ · · · ∨ (tl
1 ∧ tl
2 ∧ · · · ∧ tl
kl
)
Similarly, a Conjunctive Normal Form (CNF) consists of a conjunction of
disjunctions of variables and their negations, also known as a product of
sums. It is of the form
(t1
1 ∨ t1
2 ∨ · · · ∨ t1
k1
) ∧ · · · ∧ (tl
1 ∨ tl
2 ∨ · · · ∨ tl
kl
)
Every Boolean expression can be represented a DNF or a CNF.
2.3 Binary Decision Diagrams
A Binary Decision Diagram (BDD) represents Boolean expressions in the
if-then-else form, given by x → y1, y2
x → y1, y2 = (x ∧ y1) ∨ (¬x ∧ y2)
An expression t → t1, t2 is true if t and t1 are true or if t is false and t2 is
true. A Boolean expression is in the If-then-else Normal Form (INF) if it
is built entirely from the if-then-else operator and the constants 0 and 1[2]
.
Thus, at each level, only single variables are evaluated and a tree is formed
called a binary decision tree. At each level, a subexpression of the original
Boolean formula is formed by substituting certain variables successively. A
BDD is thus a complete binary tree which can be constructed as a rooted,
directed acyclic graph with the following properties.
6
9. • one or two terminal nodes of out-degree zero labeled 0 or 1
• a set of variable nodes u of out-degree two. The two outgoing edges
are given by two functions low(u) and high(u). A variable var(u) is
associated with each variable node which denotes the depth of the node.
A Reduced Ordered Binary Decision Diagram is a BDD which follows a dis-
tinct ordering of variables x1 < x2 < . . . < xn. It also has the following two
properties.
• (uniqueness) no two distinct nodes u and v have the same variable
name and low and high-successor i.e.
if var(u) = var(v), low(u) = low(v), high(u) = high(v), then u = v
• no variable node u has identical low and high-successor, i.e.,
low(u) = high(u)
To represent Boolean expressions, ROBDDs are constructed which are ex-
tremely amenable to manipulation and satisfiability count (SatCount) com-
putation.
7
10. 3 Modeling the Vesicular Trafficking System
The system of vesicular trafficking is mainly governed by the following factors.
1. Fusion Molecules
(a) Fusion Activators
(b) Fusion Inhibitors
2. Budding Molecules
(a) Budding Activators
(b) Budding Inhibitors
3. Coat Proteins
In our model, we placed a few restriction on the molecular rules that describe
vesicular transport. A molecule can either be an activator or an inhibitor
but not both. We have also assumed that a molecule can either be involved
in the process of fusion or of budding, and not both. Given a n molecule
system, where k molecules are fusion molecules and the remaining n − k are
budding molecules there are 2n
possible unique compartments and similarly
the same number of vesicles. The set of molecular rules are represented as
a fusion and budding matrix, labeled F-Matrix and G-Matrix respectively.
The order of both matrices is 2n
× 2n
. As is immediately evident, increasing
the number of molecules by even one leads to quadrupling of each matrix.
At the level of 10 molecules, we are already dealing with approximately one
million entries in each matrix.
3.1 Fusion Matrix
The fusion matrix describes which fusions are possible. We seek to represent
each matrix as a Boolean expression where every variable indicates the pres-
ence or absence of the corresponding molecule. Since the same molecule can
be present or absent in either the compartment or the vesicle, two different
8
11. variables represent the presence or absence of the molecule in the (a) com-
partment, and (b) the vesicle separately.
Each matrix can be represented as a Boolean formula, and thereby con-
verted to a DNF. With the restrictions that we placed on our molecular
rules, we see that DNFs thus formed are monotonic in nature. A monotonic
function is one that is either increasing or decreasing in each of its variables
independently. This property arises because a variable in the Boolean for-
mula appears either in its positive form or negated form only, and not both.
Biologically, an activator molecule appears in the positive form, whereas an
inhibitor appears negated. A simple example of a monotonic Boolean ex-
pression in its Disjunctive Normal Form is:
(a ∧ ¬d ∧ ¬e) ∨ (b ∧ c ∧ k) ∨ (b ∧ ¬n ∧ ¬o)
In this example, a, b, c and k are activators of fusion, whereas d, e, n and o
are inhibitors.
3.1.1 Measuring SatCount and its Dependence on Activators, Clauses
and Terms
We randomly generated many Boolean expressions in their DNFs by varying
the number of molecules, number of activators, number of clauses and the
number of terms per clause. We were mainly interested in the distribution
of SatCount as a function of the number of activators.
We found that the SatCount of Boolean expressions is independent
of the number of activators. The number of activators only shifts around
the ones in the matrix and does not actually result in a change in the Sat-
Count.
We also examined the effect of number of clauses and the number of terms
per clause on the SatCount of a formula. We found that SatCount increases
as the number of clauses increases and decreases as the number of terms
decreases.
9
12. Figure 2: Mean SatCount for a 1000 randomly generated fusion Boolean expressions with 10
molecules, 5 clauses and 5 terms per clause. The SatCount is relatively steady despite the
change in number of activators.
To summarize,
SatCount ∝ Activators (1)
SatCount ∝
Clauses
Terms
(2)
3.1.2 Clustering of Ones and Zeros
We also compared our randomly generated Boolean formulae with randomly
generated matrices of the same density to understand their similarities and
10
13. Figure 3: A Matrix Walk was done (along both rows and columns) for a randomly generated
Boolean formula and it was compared with a randomly generated matrix of the same density.
The nature of the Boolean formula is such that there is significant clustering of ones and zeros.
Therefore, the plot for a Boolean formula has clear peaks. The randomly generated matrix
however remains more or less steady and near 0.
differences. We first looked at a matrix walk through both the formula as
well as the random matrix.
We define walking through a matrix as follows. Starting from the first
entry of the matrix, we move either along a row or a column. Let the number
of ones in the matrix be ones and number of zeros be zeros. We initialize a
variable sum. For every 0 we encounter, we arbitrarily add −1 to sum and
for every 1 we encounter, we add a factor equalling zeros
ones
to sum. We obtain
a plot as shown in Figure 3.
3.1.3 Number of Clauses and Terms in a Randomly Generated
Matrix of a Given Density
As we have seen earlier, the SatCount or density of a matrix depended on
the number of clauses and terms in a Boolean formula. We attempted to
find out the average number of clauses and terms if we were to convert a
random matrix to a Boolean formula in its DNF (Figure 4). We saw a blow
up of the number of terms and clauses in each formula when compared to
11
14. Boolean formulae of the same densities. This is expected because of the de-
clustering of ones and zeros in a random matrix. Because these ones and zeros
are distributed evenly, no distinct pattern is found in their corresponding
Boolean formulae.
Figure 4: We chose a particular density for a matrix and generated 100 such random matrices.
We converted each of them to a Boolean formula and simplified them using the QM method.
The plot shows the number of clauses we obtained for different densities.
3.2 Budding Matrix
Apart from budding molecules, the budding formula depends on coat pro-
teins as well. Each coat protein has two properties: (a) a recruitment DNF;
and (b) a Nc String . The recruitment DNF tells the coat protein which
compartments it can attach to, and the Nc String dictates which molecules
it can pick from the compartment. All possible subsets of the Nc string are
packed into a vesicles from each compartment. If multiple coats can attach
themselves to a compartment, then each compartment will give away many
different types of vesicles.
Each G-Matrix tells us which vesicles can be given away from each compart-
ment. Together with the F-Matrix, we can trace the complete path of a cell
state till it reaches a steady state.
12
15. Consider an n molecule system. Let the vesicle variables be V1, V2, . . . , Vn
Figure 5: Mean SatCount for a 1000 randomly generated budding Boolean expressions with 7
molecules, 3 clauses, 3 terms per clause and 3 coat proteins. The SatCount is relatively steady
(as with fusion formulae) despite the change in number of activators.
and the compartment variables to be C1, C2, . . . , Cn. Let there be k coat
proteins. Then, the Nc string for each coat is a binary string represented
by (Nc1
1, Nc1
2 . . . Nc1
n), . . . , (Nck
1, Nck
2 . . . Nck
n) respectively. Each G-formula
is of the form
((V1 ⇔ (C1 ∧ Nc1
1)) ∧ (V2 ⇔ (C2 ∧ Nc1
2)) ∧ · · · ∧ (Vn ⇔ (Cn ∧ Nc1
n)))
∨ ((V1 ⇔ (C1 ∧ Nc2
1)) ∧ (V2 ⇔ (C2 ∧ Nc2
2)) ∧ · · · ∧ (Vn ⇔ (Cn ∧ Nc2
n)))
...
∨ ((V1 ⇔ (C1 ∧ Nck
1)) ∧ (V2 ⇔ (C2 ∧ Nc2
2)) ∧ · · · ∧ (Vn ⇔ (Cn ∧ Nck
n)))
The recruitment DNFs are very similar in structure to the F-formulae. For
instance,
(C1 ∧ C3 ∧ ¬C7) ∨ (C2 ∧ ¬C9 ∧ ¬C8)
13
16. G-Formulae consequently have a higher degree of complexity and are not
simple DNFs as was the case with fusion formulae. However, we observe
that SatCount even for the budding formulae does not depend on the num-
ber of activators. Thus,
SatCount ∝ Activators (3)
A sample plot of SatCount as a function of the number of activators is shown
in Figure 5. The G-matrix however is much more sparse than the F-matrix
at the same number of molecules.
14
17. 4 Hybridization of Fusion Formulae
Very often, two different cells having similar molecular rules fuse together.
This leads to a rather interesting phenomenon and allows us to understand
the evolution of these rules. We represent the molecules in the two sets of
cells as separate variables or entities. If the two molecules are identical or can
be substituted for one another, there will be no perturbation of the molecular
rules. However, if these two molecules are, in fact, independent, it will result
in some perturbation of molecular rules.
We study these perturbations again through the SatCount of the hybridized
Figure 6: Normalized SatCount as a function of the Degree of Crosstalk. The blue line indicates
the SatCount whereas the red line shows SatCount
SatCount at Crosstalk 100% . In some cases, we observed
that the SatCount was indeed maximum at a degree of crosstalk of 100%, whereas in other
cases we did not find this to be the case.
formulae. Consider two formulae:
(a1 ∧ b1 ∧ c1)
and
(a2 ∧ b2 ∧ c2)
If these formulae are hybridized, and a1 and a2 are identical, we would get
((a1 ∨ a2) ∧ b1 ∧ c1)
15
18. Figure 7: Normalized SatCount of a Budding formula as a function of the Degree of Crosstalk.
These plots are much more haphazard than those of the Fusion formulae.
Figures 6 and 7 show plots of Normalized SatCount as a function of the
degree of crosstalk for fusion formulae and budding formulae respectively.
We find no clear pattern in either of these to predict a trend.
16
19. 5 Ongoing Work
Having understood how Boolean formulae and their properties are affected by
changes in parameters such as activators, clauses, terms, and coat proteins,
we have turned our attention to Cell States. A cell state is described by the
combination of compartments it has along with a specific F- and G-Matrix.
With a n molecule system, there are 22n
possible cell states.
A layer in a Cell State space is defined by the number of unique molecules
and the number of comparments. A n molecule, m compartment layer con-
sists of all combinations of cell states with n unique molecules in m different
compartments.
In any layer, we find three types of nodes - self nodes, exit nodes and
transit nodes. Self nodes link back to themselves, exit nodes lead out of
that layer (that is, the number of molecules or compartments decreases)
and transit nodes lead to other nodes in the same layer. Using randomly
generated matrices, we find that the percentage of self nodes and exit nodes
is very huge. While the percentages vary from one set of matrices to another,
we find that there are very few transit nodes in a layer. This is a slightly
disturbing fact because it means that either most nodes in that layer lead
out of it, or most cell states are trivial; they do not interact with other
compartments and do not undergo any updates. We also found that the
average path length to reach a self node was close to 1. Thus, we are now
looking at generating more realistic matrices. One of the parameters we are
investigating is the correlation between two compartments in a matrix.
17
20. References
[1] Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith
Roberts, and Peter Walter. Molecular Biology of the Cell, 4th edition.
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[2] Henrik Reif Andersen. An introduction to binary decision diagrams. 1997.
[3] Mordechai Ben-Ari. Mathematical Logic for Computer Science, 3rd edi-
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[4] Juan S. Bonifacino and Benjamin S. Glick. The mechanisms of vesicle
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[5] Frances M. Brodsky, Chih-Ying Chen, Christine Knuehl, Mhairi C.
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18