Interplay between cortical adhesion and membrane bending regulates microparticle formation
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The formation of blebs and microparticle formation requires the bending of the plasma membrane away from the cytosol. There are multiple factors that control the formation of the microparticles including the loss of lipid asymmetry, primarily the exposure of phosphatidylserine on the outer leaflet, detachment of the membrane from the cortical cytoskeleton, and bleb expansion due to pressure. In this work, we develop a biophysical model that accounts for the interaction between these different factors. Our findings reveal that linker attachment is a key determinant of outward budding and lays out the mechanical aspects of outward budding of the plasma membrane.
Significance Statement
Cells release many types of membrane-enclosed vesicles in response to stress, inflammation, or other injuries. Formation of these membrane-enclosed structures is critical for proper function of the coagulation cascade and apoptosis. In many cases, these microparticles are also a part of the long distance intercellular communication and are implicated in chemoresistance. A particular class of vesicles called ectosomes or microparticles are released by the outward budding of the plasma membrane, a process which requires detachment of the membrane from the cortex, exposure of negatively charged, curvature-inducing lipids such as phosphatidylserine from the inner leaflet to the outer leaflet, and pressure-driven expansion of the bleb. Here, we used membrane mechanics coupled with the kinetics of adhesive linker binding-unbinding to investigate how these different factors interact together. Using our models, we predict how linker properties plays an important role in the outward budding of the plasma membrane and identify conditions that can promote or inhibit such curvature generation. These findings have implications not just for conditions that require successful microparticle formation such as the procoagulation cascade but also for inhibiting microparticle formation in cases of chemoresistant drug efflux by tumor cells.
