Polar pattern formation induced by contact following locomotion in a multicellular system

Abstract

<jats:title>Abstract</jats:title><jats:p>Biophysical mechanisms underlying collective cell migration of eukaryotic cells have been studied extensively in recent years. One paradigm that induces cells to correlate their motions is contact inhibition of locomotion, by which cells migrating away from the contact site. Here, we report that tail-following behavior at the contact site, termed contact following locomotion (CFL), can induce a non-trivial collective behavior in migrating cells. We show the emergence of a traveling band showing polar order in a mutant <jats:italic>Dictyostelium</jats:italic> cell that lacks chemotactic activity. The traveling band is dynamic in the sense that it continuously assembled at the front of the band and disassembled at the back. A mutant cell lacking cell adhesion molecule TgrB1 did not show both the traveling band formation and CFL. We thus conclude that CFL is the cell-cell interaction underlying the traveling band formation. We then develop an agent-based simulation with CFL, which shows the role of CFL in the formation of traveling band. We further show that the polar order phase consists of subpopulations that exhibit characteristic transversal motions with respect to the direction of band propagation. These findings describe a novel mechanism of collective cell migration involving cell–cell interactions capable of inducing traveling band with polar order.</jats:p>

Learning the dynamics of cell–cell interactions in confined cell migration

“…By inhibiting intracellular Rho signaling in neural crest cells, this reversal-dominated behavior could be tuned to following-dominated behavior (34). Such following behav-ior has also been identified as an important mechanism in collective migration (12,20,21,54) and was termed contact following locomotion (20). Finally, previous work has shown that reducing the expression levels of E-cadherin enables otherwise reversing cells to mainly slide past each other (19).…”

“…These cellular interactions depend on complex molecular mechanisms, including cadherin-dependent pathways and receptor-mediated cell-cell recognition (5,10,11,(14)(15)(16)(17). At the cellular scale, this molecular machinery leads to coordinated, functional behaviors of interacting cells (3,(5)(6)(7)(8)(9)(10), which are highly variable and may take distinct forms in different biological contexts (10,(18)(19)(20)(21).…”

Collective cell migration driven by filopodia—New insights from the social behavior of myotubes

“…A self‐regulated contact‐dependent behavior—not directly related to CSM—is contact following locomotion (CFL), also termed contact activation of migration. [ 92–94 ] CFL is a co‐attractive cue, discovered in cultured cells on micropatterned stripes. When a cell contacts the trailing edge of another cell, it gets chemically attracted.…”

Interplay of mesoscale physics and agent-like behaviors in the parallel evolution of aggregative multicellularity

“…In Dictyostelia, the cells are embedded in cellulose-based matrices that enable cell rearrangement and hence the liquid-like behaviors described above [ 50 ]. However, the lack of direct engagement with the cytoskeleton in this attachment mode makes cell polarization, even when it occurs, transient and unconducive to lumen formation or stable intercalation ([ 65 ]; however, see [ 66 ]). Cells of Dictyostelia also have a more pronounced chemotactic response to extracellular signals than most animal embryonic cells, which contributes to their particular version of liquid-tissue properties [ 67 ] (see below).…”

“…In some cases, however, developmental transformations cannot be attributed to either category of effect alone, but can only be understood as outcomes of a combination of the two acting in concert. A newly characterized example of this described by Hayakawa et al [ 66 ], in which an ordered, liquid crystalline-like field of polarized D. discoideum amoebae organizes by phase separation from populations of cells of a mutant strain incapable of chemotactic signaling via cAMP. This novel patterning phenomenon, which has generic-type features, occurs by “contact following locomotion”, a behavior whose agent-type role in the collective motion is supported by simulations.…”