Physical minimal models of amoeboid cell motility

Cell locomotion plays an important role in many biological processes such as the immune system, embryonic development, or cancer metastasis. In these examples, cells interact with their environments or coordinate their movements with other cells, creating collective behavior. In this thesis, we utilize minimal modeling to investigate single and collective cell motility in three different settings. The key question we strive to answer is whether cell locomotion is a physical process that can function without the biochemistry that controls it. First, we examine contact inhibition of locomotion (CIL), which is one of the ways that cells interact. In experiments, cell migration can be restricted to quasi-one-dimensional stripes. In these stripes, head-on collisions of two cells occur frequently with only a few outcomes, such as cells reversing their directions, sticking to one another, or walking past each other. By utilizing a phase field model that includes the mechanics of cell shape and a minimal chemical model for CIL, we are able to reproduce all cases seen in these collisions. In addition, we found qualitative agreements such as the occurrence of ``cell trains''. Next, we investigate cells migrating on substrates with heterogeneous rigidity. By utilizing substrate configurations where cells with varying propulsion strength and membrane stiffness behave differently, we demonstrate that heterogeneous substrates are able to sort and distinguish those cells. Further, we investigate collective interactions and reproduce collective phenomena such as persistent rotational motion. We then study flow-driven amoeboid motility that is exhibited by microplasmodia of physarum. This motion is caused by a feedback loop between a chemical regulator, active mechanical deformations, and induced flows that give rise to spatio-temporal contraction patterns. We develop a poroelastic model consisting of two phases: (1) an active viscoelastic gel representing the cytoskeleton, that is permeated by (2) a fluid depicting the cytosol. Our model incorporates active contractions of the gel that are controlled by calcium. In turn, the calcium is advected with the fluid. By using free boundary conditions, nonlinear substrate friction and a nonlinear reaction kinetic for the calcium regulator, we reproduce the oscillatory motion of these microplasmodia with a net motion in each cycle. We demonstrate in all three cases that we can reproduce experimental behavior with these minimal models. This substantiates our assumption that some aspects of cell motility can be thought of as a ``physical machine'' that is controlled by the cell's biochemistry but can operate without it.

Author dc:creator

• Kulawiak, Dirk Alexander

Advisor dc:contributor.advisor

• Engel, Harald

Licence dc:rights.uri

• https://creativecommons.org/licenses/by/4.0/

Language dc:language.iso

en

Identifier URI

http://dx.doi.org/10.14279/depositonce-6613

OAI identifier oai:identifier

oai:depositonce.tu-berlin.de:11303/7349