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

TL;DR

This study reveals that a membrane-driven pearling instability, similar to the classical Rayleigh-Plateau instability, governs the formation and fragmentation of proplatelets into platelets, providing a mechanobiological regulation mechanism.

Contribution

It demonstrates that membrane mechanics induce pearling instability in biological proplatelets, elucidating a physiological example of this phenomenon and linking physics with platelet biogenesis.

Findings

Pearling occurs during proplatelet extension in blood vessels.

Theoretical predictions match experimental observations without adjustable parameters.

Pearling regulates platelet size and release timing.

Abstract

At the end of the 19th century, Rayleigh and Plateau explained the physical principle behind the fragmentation of a liquid jet into regular droplets commonly observed in everyday life from a faucet. 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 recognised 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 in the bone marrow by the extension of long protrusions, called proplatelets, that traverse the blood vessels. As they extend in the bloodstream, proplatelets become pearled and detach. Long and pearled proplatelets then circulate in the peripheral blood before their fragmentation into calibrated platelets. We propose that this pearling, by creating regular constrictions along the proplatelet, 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.