Entropic depletion of macromolecular solutes induces symmetry-breaking surface wrinkling in myelin figures

Abstract

Smectic liquid crystals, including multilamellar stacked lipid bilayers, strongly resist compression along the normal layer but bend readily. When mechanically stressed—such as by dehydration, osmotic stress, physical confinement, or even electric fields—they release elastic compressive energy by buckling into undulatory surface patterns reminiscent of the well-known Helfrich-Hurault instability. Although documented extensively for lamellar liquid crystals, observations of the Helfrich-Hurault instability in cylindrical smectic liquid crystals are scant. Here, we investigate the behavior of myelin figures—cylindrical smectic-A liquid crystals consisting of thousands of concentric amphiphilic bilayer lamellae separated by aqueous channels—when subjected to mechanical compression by the hyperosmotic stress from the osmolyte-laden surrounding bath. We find that the colligative ideal osmotic pressure exerted by small molecular osmolytes alone is insufficient to induce long-lived, surface instabilities. Using real-time optical and confocal fluorescence microscopy, we show that exposure to hypertonic solutions of low-molecular-weight osmolytes (e.g., sucrose and glycerol) leaves myelin surfaces largely smooth, even at elevated osmotic pressures. By contrast, solutions containing macromolecular osmolytes such as polyethylene glycol and dextran trigger pronounced symmetry-breaking surface instabilities in bundles of juxtaposed myelins. These instabilities manifest as long-wavelength, quasi-sinusoidal corrugations that propagate axially and preferentially localize at inter-myelin interfaces. Quantitative analysis reveals that the wavelength and amplitude of the corrugations depend on osmolyte size, even at nominally identical osmotic pressures, further implicating excluded-volume effects. Fluorescently labeled osmolytes are excluded from corrugated interfacial regions, supporting a depletion-driven mechanism. We propose that macromolecular osmolytes generate colligatively non-ideal osmotic stresses and entropic depletion forces that stabilize interlocking surface undulations by increasing the free volume available to the depletants. These findings identify solute entropy and excluded-volume interactions as key drivers that stabilize Helfrich-Hurault-type undulatory instabilities in cylindrical smectics. They further suggest a general physical mechanism by which macromolecular crowding can induce large-scale structural remodeling in soft, multilamellar systems relevant to both synthetic materials and biological assemblies.