Optimizing micropattern geometries for cell shape and migration with genetic algorithms

Abstract

Adhesive micropatterns have become a standard tool to control cell shape and function in cell culture. However, the variety of possible patterns is infinitely large and experiments often restrict themselves to established designs. Here we suggest a systematic method to establish novel micropatterns for desired functions using genetic algorithms. The evolutionary fitness of a certain pattern is computed using a cellular Potts model that describes cell behavior on micropattern. We first predict optimal patterns for a desired cell shape. We then optimize ratchet geometries to bias cell migration in a certain direction and find that asymmetric triangles are superior over the symmetric ones often used in experiments. Finally we design geometries which reverse the migration direction of cells when cell density increases due to cell division.

Physical models of collective cell motility: from cell to tissue

“…Interestingly, this consequence of displacement alignment is also implied by models generated by detailed tracking of human keratinocytes [36], as [42] notes. More recent papers have applied both velocity alignment and displacement alignment [70, 117, 66, 118, 119]. A related model of “mechanotaxis” has been used by [67], in which cells polarize in the direction of the time-averaged net force exerted on them.…”

The Research Advance of Cell Bridges in vitro

“…Furthermore, the bridging behavior did not trigger the expression of desmin, osteocalcin, alkaline phosphatase (ALP), and alizarin in hMSCs (Zhang et al, 2015b). Notably, the cell bridges are tightly coupled with cell migration (Albert and Schwarz, 2016b) and wound repair (Hu et al, 2017). Although chemical micropattern and topographic cues on substrates can regulate cell fate (Anselme et al, 2010;Jing et al, 2016) through stressing effect on focal adhesion (Abagnale et al, 2015), cell shape, cytoskeletal tension, and RhoA signaling (McBeath et al, 2004), there is a paucity of studies on the mechanism and effect of cell bridges phenomenon on properties of cells, such as stiffness, proliferation, and differentiation.…”

Cellular Response to Surface Morphology: Electrospinning and Computational Modeling

“…The model predicted, for example, that for a cell dividing on a L shaped pattern, the two daughter cells were most likely to be located on the two arms of the L, as confirmed by experimental results. In order to identify the optimal adhesive patterns to control cell functions, CPM was combined with genetic algorithms (GAs) (Albert and Schwarz, 2016c ) (Figure 2 ), which are computational techniques inspired by natural evolution for the heuristic search of problem solutions (McCall, 2005 ). The migration of cells on rachet micropatterns in a linear arrangement was analyzed and the algorithm predicted that a triangular shape was ideal to guide cell migration in the direction of the tip of the triangle, as also demonstrated experimentally.…”

“…(B) CPM can be used to predict cell shape on a microstructure, and genetic algorithms can help to define pattern geometry. Reproduced with permission from Albert and Schwarz ( 2016c ). Copyright 2016 of the Royal Society of Chemistry.…”