Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence

Abstract

Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.

Modeling Active Cell Movement With the Potts Model

“…On the other hand, bell-shape distributions were observed when τ = 1 or in a crowded neighborhood. Both bell-and crater-shape distributions for cell velocity have been predicted by a mathematical model that considers the actin flow [47], connecting persistent motion with crater-shape distribution, in agreement with our findings. Also, we observe in our simulations at low density cultures that the temporal autocorrelation of the cell velocity obtained for φ = 0.99 decays exponentially, while for high density and/or φ = 0.95 the behavior deviates from the expected random motion under the traditional Ornstein-Uhlenbeck process.…”

“…Thus, the presence of a gap in the center of the velocity distribution is associated with effective persistent cell movement, in agreement with Maiuri et al (Figure 4D of [47]). On the other hand, in high density simulations the crater-like effect is less evident (Figure 4B and Supplementary Figure 1).…”

Local Ras activation, PTEN pattern, and global actin flow in the chemotactic responses of oversized cells

“…As demonstrated by this reporter, a signalling molecule transported by a directed flow will accumulate at the tail of the cell, which is distinct from diffusion that would result only in a uniform concentration. In mammalian cells, the maintenance of cell polarity is coupled by a positive-feedback loop to the velocity of an actin flow that transports polarisation cues, and thus causes an asymmetry of their distribution depending on their affinity to actin (Maiuri et al, 2015).…”

Toward the reconstitution of synthetic cell motility

“…In the case of cells, fluctuations in myosin contractility and cell adhesion can trigger cell motility, and a positive feedback between actin retrograde flows and gradients in contractility maintains stable cell polarization. [51][52][53][54] The use of cell extracts limited the possibilities of changing the physico-chemical parameters of the medium. Cell extracts were thus replaced with a medium of purified proteins.…”

“…93 A negative feedback between myosin contractility and FAs adhesion, combined with positive feedbacks between myosin contractility, F-actin retrograde flow and network disassembly, was proposed to maintain cell polarity and promote fast and persistent movement. [51][52][53] Myosin contractility also plays a major role in bleb-based amoeboid migration. In that case cell movement is driven by actin cortex contractility where positive feedback between rearward F-actin cortical flows and gradients in myosin contractility maintains stable-bleb cell polarization and motion.…”