Tethering, evagination, and vesiculation via cell-cell interactions in microvascular flow

Vesiculation is a ubiquitous process undergone by most cell types and serves a variety of vital cell functions; vesiculation from erythrocytes, in particular, is a well-known example and constitutes a self-protection mechanism against premature clearance, inter alia. Herein, we explore a paradigm that red blood cell derived vesicles may form within the microvascular, in intense shear flow, where cells become adhered to either other cells or the extracellular matrix, by forming tethers or an evagination. Adherence may be enhanced, or caused, by diseased states or chemical anomalies as are discussed herein. The mechanisms for such processes are detailed via numerical simulations that are patterned directly from video-recorded cell microflow within the splenic venous sinus (MacDonald et al. 1987), as included, e.g., as Supplementary Material. The mechanisms uncovered highlight the necessity of accounting for remodeling of the erythrocyte's membrane skeleton and, specifically, for the time scales associated with that process that is an integral part of cell deformation. In this way, the analysis provides pointed, and vital, insights into the notion of what the, often used phrase, cell deformability actually entails in a more holistic manner. The analysis also details what data are required to make further quantitative descriptions possible and suggests experimental pathways for acquiring such.