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

Abstract

M any physiological and pathological processes involve directed cell motion. In general, migrating cells are represented with a polarized morphology with extending and retracting protrusions at the leading edge. However, cell motion is a more complex phenomenon. Cells show heterogeneous morphologies and high protrusive dynamics is not always related to cell shape. This prevents the quantitative prediction of cell motion and the identification of cellular mechanisms setting directionality. Here we discuss the importance of protrusion fluctuations in directed cell motion. We show how their spatiotemporal distribution and dynamics determine the fluctuations and directions of cell motion for NIH3T3 fibroblasts plated on micro-patterned adhesive ratchets. 1 We introduce efficient protrusions and direction index which capture short-term cell motility over hours: these new read-outs allow the prediction of parameters characteristic for the long-term motion of cells over days. The results may have important implications for the study of biological phenomena where directed cell migration is involved, in morphogenesis and in cancer.

Quasi-periodic migration of single cells on short microlanes

“…Then, if the cell can adhere in the explored region, these protrusions form stable lamellipodia through a self-reinforcing feedback loop. Note that our computational implementation conceptually resembles the protrusion fluctuation model used to describe directed cell motion on microratchets [38,39]. Therefore, the general mechanism is the dynamics and reinforcement of exploring protrusions at both ends of the cell.…”

“…There, a universal relation between persistence and cell velocity was shown to hold [7]. Other micropatterns with non-trivial geometries give rise to novel migratory behavior: circular adhesion islands lead to rotational migration of small cohorts of cells [36], ratchet geometries induce directed migration [37][38][39], cells confined in dumbbell-shaped micropatterns undergo repeated stochastic transitions characterized by intricate nonlinear migratory dynamics [40], and microlanes with gaps show emergence of stochastic cell reversal and transits [41]. In addition, migration patterns may change upon interference with the cytoskeleton.…”

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.…”

The Biophysics of Cell Migration: Biasing Cell Motion with Feynman Ratchets

“…By doing this, critical mechanisms of cell migration have been revealed and modeled, making significant contributions to biology (27). Similarly, new experimental approaches have been developed to accurately investigate directed cell motion in the absence of long-range gradients, and novel cell locomotion modes have been reported (Appendix A) (6,(29)(30)(31)(32)(33)(34)(35). These works have benefited from progress in micro-and nanofabrication techniques, optical imaging, and quantitative cell biology tools, as well as from the introduction of descriptive physical modeling.…”