Soft Matter inspired systems for modelling cell adhesion

Cell adhesion is an extremely complex phenomenon controlling a large number of impor- tant biological processes, such as tissue formation, the response of the immune system and the migration of metastatic cancerous cells. It is regulated by the interplay between specific and reversible ligand-receptor bond formation between protein pairs and non-specific repul- sive forces, mainly mediated by a negatively charged polymer brush coated on the cell’s surface, usually referred to as the glycocalyx. In order to shed some light on the micro- scopic mechanisms governing cell adhesion, we propose to study simpler analogue physical system inspired by Soft Matter and Polymer physics: Ligand-Receptor Coated Colloids (LR- CCs) and PolyElectrolyte Brushes (PEBs). Specific realisation of these systems aiming at mimicking the natural counterpart will be investigated using a combination of Molecular Dynamics and Monte Carlo simulations together with advanced sampling techniques, e.g. Metadynamics, Wang-Landau or Non-Boltzmann sampling. Analytical or semi-analytical statistical mechanical models will be used to rationalise within a simpler framework simu- lation results. Two are the aims of the present proposal. The first is to develop a unified framework to describe ligand-receptor mediated attraction between cells, starting from the self-consistent theory recently developed by the proponent and extending it with the in- clusion of elasticity and poly-valency. The second is to gain a microscopic insight into the 1 repulsive force between cell and substrates (or other cells) induced by the cell glycocalyx as a function of its structure and environment. Overall, the goal is to provide a mechanistic perspective on cell adhesion under controllable and well defined conditions. We expect that the present project will not only advance our understanding of a biologically relevant prob- lem, but also provide an important extension to current models and techniques used in Soft Matter and Polymer Physics.

Principal investigators
Dzubiella, Joachim Prof. Dr. (Details) (Theory and Simulation of Many-body Systems)

Alexander von Humboldt-Stiftung

Duration of project
Start date: 05/2013
End date: 04/2015

Last updated on 2022-08-09 at 23:07