A semi-rigid filament confined in a soft vesicle of similar size can mutually deform each other. An important example from biological context is Hemoglobin-S (HbS) fibers which polymerize inside red blood cell (RBC). The fibers deform the healthy RBC into sickle-like shape causing difficulty in blood flow through capillaries. Using an area difference elasticity (ADE) model for RBC and a worm-like chain model for the HbS fibers, confined within RBC, we study the shape deformations at equilibrium. We also consider multiple filaments and find that confinement can generate multipolar RBC shapes and can also promote helical filament conformations. The same model, in different parameter regime, reproduces tubulation for phospholipid vesicles, as seen in experiments, when microtubules are confined in the vesicle. We conclude that with a decrease in the surface area to volume ratio, and membrane rigidity, the vesicle prefers tubulation over sickling. Our simulations can access various non-axisymmetric shapes, which have been observed experimentally, both in the context of sickle RBC and phospholipid vesicles, but have so far remained beyond the scope of variational methods.
PACS numbers:Shape of animal cells and their functions are interrelated. Abnormal cell shape can lead to pathological situations. For example, healthy, red blood cells (RBC) smoothly flow through our circulatory system, where as deformed, sickle shaped RBC cannot pass through capillaries, the thinnest of the blood vessels in our body, giving rise to sickle cell disease. The deformation is caused by semi-rigid Hemoglobin fibers that push the RBC membrane from inside. The fibers grow due to abnormal polymerization of Hemoglobin-S (HbS) molecules and the polymerization is triggered by oxygen deficiency in the blood of patients who have certain genetic defects. Fig.1A shows variety of deformed RBC shapes that are found during sickling and here we ask how the fibermembrane interaction gives rise to such shapes.Each HbS fiber, which we will henceforth refer to as filament, is made of seven double strands of HbS molecules [1] interwined into a twisted structure. Cryo-electron microscopy (CryoEM) has revealed [2] that, inside RBC, HbS fibers occur both as single filament as well as in a bundle form. Possibility of heterogeneous nucleation on these bundles resulting in branched structures has also been considered [3] in the literature. In addition, the organization of the cytoskeleton underlying the RBC membrane may also change [4] during sickling. Here we will focus on elastic deformations of RBC purely due to stiff filaments or filament bundles, confined inside.A related problem, namely, in vitro polymerization of microtubules (MT) inside phospholipid vesicle and resulting deformations of the vesicle, offers useful insight [5][6][7]. This is despite the obvious dissimilarity that phospholipid vesicles when pushed from inside by MT filaments, develop tubular protrusions, which is not seen in RBC sickling. We will show that the same model can be used for both ...