Biology subjects

Mogilner, A.

Publications and source records attributed to Mogilner, A..

3 recordsLinked to original sources

bioRxiv2018

Cell Mechanics at the Rear Act To Steer the Direction of Cell Migration

Motile cells navigate complex environments by changing their direction of travel, generating left-right asymmetries in their mechanical subsystems to physically turn. Currently little is known about how external directional cues are propagated along the length scale of the whole cell and integrated with its force-generating apparatus to steer migration mechanically. We examine the mechanics of spontaneous cell turning in fish epidermal keratocytes and find that the mechanical asymmetries responsible for turning behavior predominate at the rear of the cell, where there is asymmetric centripetal actin flow. Using experimental perturbations we identify two linked feedback loops connecting myosin II contractility, adhesion strength and actin network flow in turning cells that are sufficient to recreate observed cell shapes and trajectories in a computational model. Surprisingly, asymmetries in actin polymerization at the cell leading edge play only a minor role in the mechanics of cell turning - that is, cells steer from the rear.\n\nHighlightsO_LIFish keratocytes can migrate with persistent angular velocity, straight or in circles.\nC_LIO_LIAsymmetry in protrusion at the leading edge is not sufficient to generate persistent turning.\nC_LIO_LIAsymmetries in myosin II contraction, actin flow and adhesion at the cell rear cause turns.\nC_LIO_LIOur new computational model of migration predicts observed cell trajectories.\nC_LI

cell biology↗

bioRxiv2018

Reconstitution of the equilibrium state of dynamic actin networks

Principles of regulation of actin network dimensions, fundamentally important for cell functions, remain unclear. We studied in vitro and in silico the effect of key parameters, actin density, ADF/Cofilin concentration and network width on the network length. In the presence of ADF/Cofilin, networks reached equilibrium and became globally treadmilling. At the trailing edge, the network disintegrated into large fragments. A mathematical model predicts the network length as a function of width, actin and ADF/Cofilin concentrations. Local depletion of ADF/Cofilin by binding to actin is significant, leading to wider networks growing longer. A single rate of breaking network nodes, proportional to ADF/Cofilin density and inversely proportional to the square of the actin density, can account for the disassembly dynamics. Selective disassembly of heterogeneous networks by ADF/Cofilin controls steering during motility. Our results establish general principles on how the dynamic equilibrium state of actin network emerges from biochemical and structural feedbacks.

cell biology↗

bioRxiv2018

Infection-generated electric field in gut epithelium drives bidirectional migration of macrophages

Many bacterial pathogens hijack macrophages to egress from the port of entry to the lymphatic/blood-stream, causing dissemination of life-threatening infections. However, the underlying mechanisms are not well understood. Here, we report that Salmonella infection generates directional electric fields (EF) in the follicle-associated epithelium of mouse cecum. In vitro application of an EF, mimicking the infection-generated electric field (IGEF), induces directional migration of primary mouse macrophages to the anode, which is reversed to the cathode upon Salmonella infection. This infection-dependent directional switch is independent of the Salmonella pathogenicity island 1 (SPI-1) type III secretion system. The switch is accompanied by a reduction of sialic acids on glycosylated surface components during phagocytosis of bacteria, which is absent in macrophages challenged by microspheres. Moreover, enzymatic cleavage of terminally exposed sialic acids reduces macrophage surface negativity and severely impairs directional migration of macrophages in response to EF. Based on these findings, we propose that macrophages are attracted to the site of infection by a combination of chemotaxis and galvanotaxis; after phagocytosis of bacteria, surface electrical properties of the macrophage change, and galvanotaxis directs the cells away from the site of infection.\n\nAbbreviationsCFU, colony-forming unit; Con A, Concanavalin A; EF, electric field; FAE, follicle-associated epithelium; GNL, Galanthus Nivalis lectin; IGEF, infection-generated electric field; Ji, electric current density; MAL-2, Maackia Amurensis lectin II; MLN, mesenteric lymph node; MOI, multiplicity of infection; nMFI, normalized mean fluorescence intensity; RCA-1, Ricinus Communis Agglutinin I; SNA, Sambucus Nigra lectin; S. Typhimurium, Salmonella enterica serotype Typhimurium; SPI-1, Salmonella pathogenicity island 1; PDMS, polydimethylsiloxane; TEP, trans-epithelial potential difference; TLR, Toll-like receptors; WGEF, wound-generated electric field

cell biology↗