Tube into pearls: A membrane-driven pearling instability shapes platelet biogenesis.

At the end of the 19th century, Rayleigh and Plateau explained the physical principle behind the fragmentation of a liquid jet into regular droplets. The classical Rayleigh-Plateau instability concerns liquid jets governed by inertia and surface tension, whereas biological tubes are membrane-bounded and inertia-free. We therefore refer to the process observed here as a pearling instability, formally analogous to Rayleigh-Plateau but dominated by membrane mechanics. Although pearling-type instabilities have long been recognized in lipid tubes and some biological systems, a clear physiological example remained elusive. Here, we present results showing that pearling instability occurs during the physiological process of platelet formation. Platelets are formed from megakaryocytes by the extension of long protrusions, called proplatelets. As they extend in the bloodstream, proplatelets become pearled and detach, circulating in the peripheral blood before their fragmentation into calibrated platelets. We propose that this pearling, by creating regular constrictions along proplatelets, is key to the process of proplatelet fragmentation into individual platelets of calibrated size. Pearling instability thus acts as a mechanobiological regulator allowing local delivery of the right size platelets to the right place at the right time. Our observations quantitatively match parameter-free theoretical predictions for membrane pearling, supporting a unified physical picture.