Cells as Active Particles in Asymmetric Potentials: Motility under External Gradients

Abstract

Cell migration is a crucial event during development and in disease. Mechanical constraints and chemical gradients can contribute to the establishment of cell direction, but their respective roles remain poorly understood. Using a microfabricated topographical ratchet, we show that the nucleus dictates the direction of cell movement through mechanical guidance by its environment. We demonstrate that this direction can be tuned by combining the topographical ratchet with a biochemical gradient of fibronectin adhesion. We report competition and cooperation between the two external cues. We also quantitatively compare the measurements associated with the trajectory of a model that treats cells as fluctuating particles trapped in a periodic asymmetric potential. We show that the cell nucleus contributes to the strength of the trap, whereas cell protrusions guided by the adhesive gradients add a constant tunable bias to the direction of cell motion.

The cell ratchet: Interplay between efficient protrusions and adhesion determines cell motion

“…Cells were shown to migrate directionally in systems were the spatial symmetry was broken and in the absence of any environmental cue. [22][23][24] Cells deposited on ratchet-like microchannels or under tilted micropillars were shown to migrate by mechanically interacting with the environment. Clearly, symmetry can be broken by many means.…”

Chemotaxis and topotaxis add vectorially for amoeboid cell migration

“…al. 17 (hapto-vs topotaxis). Although not explicitly analyzed as such in their study, the presented cell migration data in an assay consisting of both a ratchet (topotaxis) and a fibronectin gradient (adhesional haptotaxis) seems to indicate linear addition of these cues as well.…”

“…The physical structure of the micro-environment around the cell, the 3D-topography, can act as a stimulus modulating cell direction and speed during migration 6 . In vitro topographical structures are typically made up out of channels [12][13][14][15] , ratchets [16][17][18] , grooves [19][20][21] , pillars [22][23][24] , curves 25 , or areas with increased alignment of extracellular matrix fibers 14,[26][27][28] . These topotaxis assays rely on topographical asymmetries, and exploit differences in slope, confinement or alignment to influence cell migration.…”

“…The potential interplay between topographical and chemical guidance cues has not been studied extensively (cf. Comelles et al on topo-versus haptotaxis 17 ). Yet, such combined assays provide an excellent platform to gain insight into how multiple cues affect cell migration simultaneously.…”

Cell motion as a stochastic process controlled by focal contacts dynamics

“…Previous works showed in vitro, as a proof of a principle, that local asymmetries in cellular environment can bias cell directionality in another mode of migration named ratchetaxis (10)(11)(12)(13)(14)(15)(16)(17). This type of behavior can lead to long-term directionality and stresses the importance of stochastic probing associated to cell protrusions, as well as the role of environment topology.…”