Hybrid CPM (ECM) Flashcards
what is strain ?
relative deformation (e.g. length/area), compared to a reference position configuration
what is stress?
describes forces present during deformation. defined as the force across a small boundary per unit area of that boundary, for all orientations of the boundary. F/A
Cell area decreases with substrate stiffness.
True or False
False
The cell anchors more strongly on the substrate due to the focal adhesions and consequentially it gets more spread out.
Describe the three general steps of a CPM hybrid model + ECM
CPM-> Traction forces -> Focal Adhesions
How does an ECM hybrid CPM acount for cell elongation?
additional step of a finite element model (FEM) which creates a tensile force on the cell as a ECM stress response.
What is durotaxis?
Directional movement following a mechanical stiffness gradient.
If a cell is placed on a substrate with mechanical stiffness gradient present how will it respond and why?
Durotaxis. As it will adhere more strongly to stiffer spaces of the substrate it will slowly move towards the stiffer most area of the substrate
What is the biggest downside of a FEM model of a ECM?
It assumes a homogeneous ECM when it most often is fibrous. Other more advanced models allow for a fibrous ECM through MD to also account for how cells adhesion pulls or pushes those fibers.
How does a CPM update happen and MD simulation of a fibrous ECM included.
The energy of the new fiber configuration has to be considered in addition to the one of the cell itself.
Why are MCS used in CPM?
To ensure the measure of time is independent of the lattice size
What is MCS?
Monte Carlo Steps = CPM Copy attempts / #gridspaces in the lattice
2 most important properties of a fibrous ECM simulation
fibre density and cross link density
what is fiber densification
the ration between density of fibers rarther and close to cell. As cells compress the tend to accumulate fibers around them.
How does crosslinking influence fiber densification?
How do you measure the change in stiffness of a fibrous ECM in MD-CPM hybrid upon cell adhesion?
in silico AFM
A grid of linear elastic pillars was placed underneath the 2D ECM thin film in order to mimic an extended medium in the third dimension. Thus, in regions with few fibers only the pillar grid provided a counterforce to probe indentation. In regions with many fibers, probe indentation was resisted by the combination of the pillar grid and the overlying fiber network.
How can you measure accurately the stiffness of a low density substrate?
Measuring segments of high and low stiffness seperately
How does the Young’s modulus of a fibrous ECM relate to the distance from a cell in this ECM.
Exponentially goes down as observed in experimental data
How does ECM stiffness affect cell-cell interactions? why?
Why? : strain formed by one cell on ECM is sensed by other cells in the same ECM. mechanical cell-cell comunication.
Describe cell-cell mechanocomunication for 0.5 kPa, 12kPa and 32kPa stiff ECM
0.5kPa: cells stick to one another and dont unbind (thus low binding counts and no proper alignment between multiple cells)
12kPa: cells align and bind much more frequently
32kPa: the increased stiffness inhibits cell comunications and cells are again not interacting
At what conditions to bound cells move more rapidly than singlke cells in an ECM environment?
high stiffness (33kPa) while at intermediate stiffness individual cells move much more rapidly
How does the tendency of cells for mechanical comunication at intermediate stiffness translate on a multicellular level?
Network formation
How does the structure of a tissue change in a ECM hybrid CPM at different stiffness levels?
How can the CPM be adapted to account for the observed persistent movement in biological tissues?
*the persistence vector p can be adjusted each step, not predefined
How to model cell movement?
Random walk? Lol no this is too simple. Cells in fact have much more persistent active motion/migration using filopodia. Filopodia formation can be modelled using coarse grained model of actin polymerization with autocatalysis of membrane protrusions/ filopodia which.
Matrix stress reinforces focal adhsions due to recruiment of stabilizing proteins. True or False
True
