There is a rich and long history of gaining inspiration from nature for the design of practical materials and systems. With the recent developments of molecular and nanoscale engineering in physical sciences, and advances in molecular biology, biomimetics is entering the molecular scale. Molecular biomimetics is an emerging field in which hybrid technologies are developed by using the tools of molecular biology and nanotechnology. For example, taking lessons from biology, polypeptides can now be engineered to specifically bind to selected compounds for applications in nano- and biotechnology. Starting from the theoretical basis recent developments obtained by the Biomechanics Group within the DEIB Department (www.biomech.polimi.it/molecular-modeling) will be described and discussed with a particular focus on the regenerative medicine field.

1. Molecular Biomimetics: Inspiration comes
naturally
Simone Vesentini
simone.vesentini@polimi.it
interno: 3480

2. Simone Vesentini
Biomimetics
Biologically inspired design or adaptation or derivation from nature is referred
to as ‘biomimetics’.
Nature in about 3.8 Gyr has developed materials, objects and processes that function
from the macroscale to the nanoscale. Hierarchical structures with dimensions of
features ranging from the macroscale to the nanoscale are extremely common in
nature to provide properties of interest.
The field of biomimetics allows one to mimic biology or nature to develop
nanomaterials, nanodevices and processes.
Properties of biological materials and surfaces result
from a complex interplay between surface morphology
and physical and chemical properties.

3. Simone Vesentini
Biomimetics
Molecular scale devices, superhydrophobicity, self-cleaning, drag reduction in fluid
flow, energy conversion and conservation, high adhesion, reversible adhesion,
aerodynamic lift, materials and fibres with high mechanical strength, biological self-
assembly, antireflection, structural coloration, thermal insulation, self-healing and
sensory-aid mechanisms are some of the examples found in nature that are of
commercial interest.

4. Simone Vesentini
Biomimetics problem-solving process

5. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation
Osteoarthritis

6. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

7. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

8. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

9. Simone Vesentini
Cartilage is a hydrated, avascular tissue composed
of ∼65–75% w/w water and ECM, as well as cartilage
cells.
Despite the critical biological function of cartilage cells
(they are responsible for the synthesis, maintenance, and turnover
of the ECM components), they do not contribute
significantly to the bulk mechanical properties of the
tissue (they make up only 3–5% of the volume of adult articular
cartilage and their stiffness is two to three orders of magnitude less
than that of the ECM).
The load-bearing capability of cartilage is sustained
primarily by two ECM components: the
fibrillar collagen network and the highly negatively
charged proteoglycan aggrecan, which account
for ∼20–30% and ∼10% of cartilage (w/w), respectively.
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

10. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

11. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

12. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

13. Simone Vesentini
Chondroitin sulphate (CS)
In a single Aggrecan molecule ~100 CS chains
Each chain is composed by 20-60 disaccaride units sulphated (C4S e C6S) or
not (C0S)
In the first case Coulomb interactions are observed between COO- e SO3
- groups
cC0S cC6ScC4S
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

14. Simone Vesentini
Nano-indentation tests
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

15. Simone Vesentini
Seog et al. – experimental study
● Gold surface and chemically
functionalized tip with GAGs
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

16. Simone Vesentini
…we use Molecular dynamics to obtain information, which are
difficult/expensive to study from experiments, such as molecular movements,
molecular interactions and change in structures.
Molecular Dynamics (MD) Simulation is a technique for modeling the motion
and interaction of atoms or molecules.
MD is a set of algorithms for simulating interactions among atoms with
proper force filed and motion integrators. During the simulation force
calculation and position/velocity update are performed. Time evolution is
calculated by using the classical mechanics framework.
The POLIMI way…..
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

17. Simone Vesentini
From Potential to Movement
For each atom in every molecule, we need:
Position (r)
Momentum (mv)
Charge (q)
Bond information (which atoms, bond angles, etc.)
To run the simulation, we need the
force on each atom.
We use the gradient of the potential
energy function.
Now we can find the acceleration.
iii amF 
VF ii 
2
2
dt
rd
m
dr
dV i
i
i


18. Simone Vesentini
What is the Potential?
A single atom will be affected by the potential energy functions of every atom
in the system:
Bonded Neighbors
Non-Bonded Atoms (either other atoms in the same molecule, or atoms from
different molecules)
bondednonbonded EERV )(

19. Simone Vesentini
In silico modelling
Graphene planes with grafted CS-GAGs (4 dimers) in a water
environment 0,15 M of Na+ and Cl-
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

20. Simone Vesentini
In silico modelling
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

21. Simone Vesentini
Results: trajectories analysis
● Higher the pressure lower the distance between the two planes
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

22. Simone Vesentini
2 dimers
C0S has a lower resistance to
compressive load
C4S e C6S have a similar
behavior
Results: sulphation type
4 dimers
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

23. Simone Vesentini
Results: sulphation type and chain length
Higher the length higher the
compression resistance
⇓
● Higher number of charged
groups
● Steric effects
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

24. Simone Vesentini
simliar behavior obtained by Seog et al.
Suphation is important
Sulphation type is not important
Chain length is important
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

25. Simone Vesentini
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

26. Simone Vesentini
Reductive
Amination
reaction
Molecular Weight
Collagen ≈ 300kDa
CS ≈ 20-30kDa
NaBH3CN = 62,84 Da
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

27. Simone Vesentini
Due to the filter
dimension the
product should
remain in the filterAbout 40% of CS has been
linked to the collagen
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

28. Simone Vesentini
Ninhydrin
assay
Evaluation of
Free Amine
Content
Concentration
(mg/mL)
Absorbance at 570
nm
0,075 3,3287 ±0,0267
collagen
Unreacted Collagen
Numer of lysine residues very
high in a single collagen
molecule
Problem
analysis
Abstract
problem
Identify revelant
biological
models
Select biological
models of
interest
Relevant
knowledge
Traspose to
technology
implementation

29. Simone Vesentini
The natural world contains infinite examples of how to achieve
complex behaviours and applications by using simple materials
in a clever way, as all organisms make use of limited raw
materials to survive.