Interplay between cortical adhesion and membrane bending regulates the formation of microparticles

Cells release vesicles that serve important roles in long-range signaling and intercellular communication. These vesicles are released not just in response to stress, inflammation, injury, and chemoresistance, but also during homeostatic regulation. A particular class of vesicles called ectosomes or microparticles are released by the outward budding of the plasma membrane, a process which requires both the detachment of the membrane from the cortex and the exposure of negatively charged, curvature-inducing lipids such as phosphatidylserine from the inner leaflet to the outer leaflet. In this work, we develop a biophysical model that accounts for the interaction between these different factors. Using our model, we predict how linker properties influence outward budding of the plasma membrane and identify conditions that can promote or inhibit membrane curvature generation. These findings provide insight into the fundamental mechanisms underlying microparticle formation, elucidating the basic biology of this critical process. Further, these mechanistic insights may inspire techniques for inhibiting microparticles where they are harmful, such as chemoresistant drug efflux by tumor cells.