Mesoscopic Rigid Body Modelling of the Extracellular Matrix Self-Assembly.

Hua Wong,Stéphanie Baud,Jessica Prévoteau-Jonquet,Nicolas Belloy,Manuel Dauchez

doi:10.1515/jib-2018-0009

Abstract

The extracellular matrix (ECM) plays an important role in supporting tissues and organs. It even has a functional role in morphogenesis and differentiation by acting as a source of active molecules (matrikines). Many diseases are linked to dysfunction of ECM components and fragments or changes in their structures. As such it is a prime target for drugs. Because of technological limitations for observations at mesoscopic scales, the precise structural organisation of the ECM is not well-known, with sparse or fuzzy experimental observables. Based on the Unity3D game and physics engines, along with rigid body dynamics, we propose a virtual sandbox to model large biological molecules as dynamic chains of rigid bodies interacting together to gain insight into ECM components behaviour in the mesoscopic range. We have preliminary results showing how parameters such as fibre flexibility or the nature and number of interactions between molecules can induce different structures in the basement membrane. Using the Unity3D game engine and virtual reality headset coupled with haptic controllers, we immerse the user inside the corresponding simulation. Untrained users are able to navigate a complex virtual sandbox crowded with large biomolecules models in a matter of seconds.

Highlights

Biologists are increasingly studying biological systems using holistic approaches such as genomics and proteomics
Online databases like the MatrixDB centralises interactions data between proteins of the extracellular matrix (ECM) [1]
We propose a multiscale approach that uses rigid body dynamics to further decrease the amount of calculation required to simulate large biological systems such as those found in the basement membrane, a layer of ECM in direct contact with cells

Summary

Introduction

Biologists are increasingly studying biological systems using holistic approaches such as genomics and proteomics. This means that a large amount of structural and interaction data becomes available. Interaction proteomics is especially focused on protein-protein interactions. Online databases like the MatrixDB centralises interactions data between proteins of the extracellular matrix (ECM) [1]. While these provide invaluable pieces of information, there is no mean to simulate/visualise these interactions and to test their behaviour in a dynamical process. Experimental observations methods have made great progress, there are still large portions of the cell or its environment, especially the ECM, that can only be observed indirectly

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