Computational modelling of cell motility modes emerging from cell-matrix adhesion dynamics

PLoS Computational Biology, vol. 18, pp. e1009156

Abstract

Lymphocytes have been described to perform different motility patterns such as Brownian random walks, persistent random walks, and Lévy walks. Depending on the conditions, such as confinement or the distribution of target cells, either Brownian or Lévy walks lead to more efficient interaction with the targets. The diversity of these motility patterns may be explained by an adaptive response to the surrounding extracellular matrix (ECM). Indeed, depending on the ECM composition, lymphocytes either display a floating motility without attaching to the ECM, or sliding and stepping motility with respectively continuous or discontinuous attachment to the ECM, or pivoting behaviour with sustained attachment to the ECM. Moreover, on the long term, lymphocytes either perform a persistent random walk or a Brownian-like movement depending on the ECM composition. How the ECM affects cell motility is still incompletely understood. Here, we integrate essential mechanistic details of the lymphocyte-matrix adhesions and lymphocyte intrinsic cytoskeletal induced cell propulsion into a Cellular Potts model (CPM). We show that the combination of de novo cell-matrix adhesion formation, adhesion growth and shrinkage, adhesion rupture, and feedback of adhesions onto cell propulsion recapitulates multiple lymphocyte behaviours, for different lymphocyte subsets and various substrates. With an increasing attachment area and increased adhesion strength, the cells' speed and persistence decreases. Additionally, the model predicts random walks with short-term persistent but long-term subdiffusive properties resulting in a pivoting type of motility. For small adhesion areas, the spatial distribution of adhesions emerges as a key factor influencing cell motility. Small adhesions at the front allow for more persistent motility than larger clusters at the back, despite a similar total adhesion area. In conclusion, we present an integrated framework to simulate the effects of ECM proteins on cell-matrix adhesion dynamics. The model reveals a sufficient set of principles explaining the plasticity of lymphocyte motility.

Authors 6

1. Leonie van Steijn Aachen Mathematical Institute

   Leiden University

   Affiliation as printed

   Mathematical Institute, Leiden University, Leiden, The Netherlands

2. Inge M. N. Wortel

   Radboud University Nijmegen

   Affiliation as printed

   Data Science, Institute for Computing and Information Sciences, Radboud University, Nijmegen, The Netherlands

3. Clément Sire

   Centre National de la Recherche Scientifique · Université Toulouse III - Paul Sabatier · Laboratoire de Physique Théorique · Université de Toulouse

   Affiliation as printed

   Laboratoire de Physique Théorique, Centre National de la Recherche Scientifique (CNRS) & Université de Toulouse-Paul Sabatier, Toulouse, France

   Laboratoire de Physique Théorique, Centre National de la Recherche Scientifique (CNRS) & Université de Toulouse—Paul Sabatier, Toulouse, France

4. Loı̈c Dupré

   Centre National de la Recherche Scientifique · Inserm · Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases · Institut Toulousain des Maladies Infectieuses et Inflammatoires · Université de Toulouse · Medical University of Vienna

   Affiliation as printed

   Department of Dermatology, Medical University of Vienna, Vienna, Austria

   Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria

   Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), INSERM, CNRS, Université de Toulouse, Toulouse, France

5. Guy Théraulaz

   Centre National de la Recherche Scientifique · Université Toulouse III - Paul Sabatier · Centre de Recherches sur la Cognition Animale · Université de Toulouse · Centre de Biologie Intégrative de Toulouse · Indian Institute of Science Bangalore

   Affiliation as printed

   Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Centre National de la Recherche Scientifique (CNRS) & Université de Toulouse-Paul Sabatier, Toulouse, France

   Centre for Ecological Sciences, Indian Institute of Science, Bengaluru, India

   Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Centre National de la Recherche Scientifique (CNRS) & Université de Toulouse—Paul Sabatier, Toulouse, France

6. Roeland M. H. Merks corresponding Aachen Institute of Biology Leiden Mathematical Institute

   Leiden University

   Affiliation as printed

   Institute of Biology Leiden, Leiden University, Leiden, The Netherlands

   Mathematical Institute, Leiden University, Leiden, The Netherlands