Local force induced conical protrusions of phagocytic cells

Abstract

Magnetic tweezers were used to study the passive and active response of macrophages to local centripetal nanonewton forces on β1 integrins. Superparamagnetic beads coated with the β1-integrin-binding protein invasin were attached to J774 murine macrophages to mimic phagocytosis of bacterial pathogens. Forces exceeding ∼0.5 nN induce the active formation of trumpet-like protrusions resembling pseudopodia after an initial elastic deflection and a response time of ∼30 seconds. The speed of advancement of the protrusion is <v>=0.065±0.020 μm second-1 and is force independent. After saturation (after about 100 seconds) the protrusion stops abruptly and is completely retracted again against forces exceeding 5 nN with an effective relaxation time of ∼30 seconds. The active protrusion is tentatively attributed to the growth of the actin cortex in the direction of the force, and evidence for the involvement of actin is provided by the finding that Latrunculin A abolishes the activated cone growth. The growth is assumed to be activated by cell signaling mediated by the invasin-specific integrins (exhibiting β1 chains) and could play a role in phagocytic and protrusive events during immune response by macrophages.

Active mechanical stabilization of the viscoplastic intracellular space of Dictyostelia cells by microtubule–actin crosstalk

“…First, mechanical material properties play a key role in the control of numerous cellular processes such as cell shape changes [1], cell locomotion [2], adhesion [3] or cell division [4] by mechanical forces. Second, local forces can control the cellular architecture in a subtle way, for instance through the activation of small GTPases of the rho-family [5] which can result in rapid (sub-second) reorganizations of the actin network [6], including the formation of stress fibres [7], the activation of micro-muscles or the growth of cellular protrusions, such as philipodia [8] or axons [9]. Finally, measurements of viscoelastic moduli provide a sensitive tool for real time studies of structural re-organizations of the cytoskeleton induced by external forces, cell signalling processes, or biochemical perturbations [7,10].…”

Viscoelasticity in Biological Systems: A Special Focus on Microbes

“…The viscoelasticity can then be probed using magnetic tweezers or magnetic twisting. The ability to functionalize magnetic colloidal beads allows for their specific localization within the cell [28,29].…”

Direct Measurement of the Force Generated by a Single Macrophage

“…Since an understanding of the mechanical properties of a cell is pivotal for understanding the mechanism of many cellular processes and cell behaviors, a broad range of research works have been conducted [1][2][3][4][5][6][7][8]. First, considering a cell as a lifeless structure, the deformability of various types of cells (red blood cells, leukocytes (white blood cell), myeloid cells, keratocytes, myoblasts, macrophages, etc.)…”

“…First, considering a cell as a lifeless structure, the deformability of various types of cells (red blood cells, leukocytes (white blood cell), myeloid cells, keratocytes, myoblasts, macrophages, etc.) has been characterized [2][3][4][5][6][7]. By these studies, mammalian cells behave as a very soft material with a typical elastic modulus of 0.5 -50 kPa.…”

“…Third, forces are not only mere external stimuli to measure the mechanical properties of a cell, but are switches that induce biologically important phenomena through so-called mechano-transduction. Upon force stimuli, the cell actually modulates the pattern of gene expression [16,17] and modifies its structure, shape, and mechanical properties [2,[18][19][20]. When a stem cell is under pressure, it is known to actually diversify into an epithelial cell.…”