Project D – Multiscale modeling of cytoskeleton and ECM

Objectives

The ultimate goal is a computational mechanotransduction model in which all biochemical and biophysical cues are combined.      This project will target the core of such a model describing mechanosensitivity through the active mechanical properties of the CSK integrated with ECM properties and focal adhesion complexes.

Description

Research in this project involves:

  • Specialization of our mesoscopic biophysical network model to the ECM component of brain tissue, featuring a hyaluronic acid network.
  • Incorporation of myosin motors in the existing actin network model by means of contractile elements whose behaviour is extracted from myosin motor dynamics described in the literature.
  • Incorporation, in a similar way, of integrins that are connected to the ECM via fibronectin, and of α-actinin as a cross-linker bundling F-actin into stress fibers. The mechanical properties of these integrators will be extracted from molecular dynamics simulations, supplemented by information on structure and dynamics from ss-NMR.