Cell Surface Area to Volume Relationship During Apoptosis and Apoptotic Body Formation

Apoptosis is a programmed form of cell death culminating in packing cell content and corpse dismantling into membrane sealed vesicles called apoptotic bodies (ABs). Apoptotic bodies are engulfed and disposed by neighboring and immune system cells without eliciting a noxious inflammatory response, thus preventing sterile tissue damage. AB formation requires a total surface area larger than the apparent, initial cell's surface area. Apoptotic volume decrease (AVD) is a two-stage process leading to an isotonic, osmotic reduction in cell water content driven by net K⁺ and Cl^- extrusion. In this article, the role of AVD is presented from a geometric point of view through the process of AB formation. AVD decisively contributes to (i) endowing the cell with the appropriate electrolytic environment for apoptotic execution; (ii) increasing the membrane surface area-to-volume ratio, along with the mobilization of membrane reservoirs (cell rounding, membrane folds and endosomal membranes), so that the cell corpse can be dismantled into ABs; and (iii) reducing plasmalemmal stretch, tension and stiffness, thus facilitating membrane bulging, blebbing and vesicle expansion ultimately leading to separation and release.