Sasidharan Sreeja, Knepper Leah, Socrier Larissa, Smits Liliane, Pash Samuel, Lowe-Krentz Linda, Thévenin Damien, Honerkamp-Smith Aurelia
Department of Physics, Lehigh University, Bethlehem, PA.
Department of Chemistry, Lehigh University, Bethlehem, PA.
bioRxiv. 2025 Aug 29:2025.08.27.672542. doi: 10.1101/2025.08.27.672542.
The rapid diffusion of membrane lipids and membrane proteins in living cell plasma membranes demonstrates that the membrane is fluid. However, motion of membrane molecules is inhibited on one side by the cytoskeletal mesh, and on the other by the glycocalyx, a layer of proteoglycans with long polysaccharide chains that covers the membrane surface. A variety of biological fluid flows (including blood circulation, cilia-driven flows, and swimming motion of microorganisms) apply shear stress to cell surfaces. Cell responses to these flows govern important physiological processes such as blood pressure and immune activation. The presence of the glycocalyx is generally thought to shield cell membranes from shear stress that arises from flow. However, here we show that two different proteins, each attached by a lipid anchor to the extracellular membrane surface of living COS-7 cells, formed reversible, cell-wide concentration gradients in the direction of applied flow. Protein redistribution occurred within minutes after we applied shear stress levels commonly found in animal cardiovascular systems. The dynamic and spatial features of these gradients were consistent with passive transport by flow. Passive flow transport could be a general mechanism for spatial organization of membrane proteins. This mechanism may explain protein patterning previously observed on flow-exposed cells, and potentially forms an initial step in flow sensing.
膜脂和膜蛋白在活细胞质膜中的快速扩散表明膜具有流动性。然而,膜分子的运动在一侧受到细胞骨架网络的抑制,在另一侧受到糖萼的抑制,糖萼是一层覆盖膜表面的带有长多糖链的蛋白聚糖。多种生物流体流动(包括血液循环、纤毛驱动的流动以及微生物的游动)会对细胞表面施加剪切应力。细胞对这些流动的反应控制着诸如血压和免疫激活等重要的生理过程。一般认为糖萼的存在可保护细胞膜免受流动产生的剪切应力。然而,我们在此表明,两种不同的蛋白质,每种都通过脂质锚定连接到活的COS - 7细胞的细胞外膜表面,在施加流动的方向上形成了可逆的全细胞浓度梯度。在我们施加动物心血管系统中常见的剪切应力水平后几分钟内就发生了蛋白质重新分布。这些梯度的动态和空间特征与流动介导的被动运输一致。被动流动运输可能是膜蛋白空间组织的一种普遍机制。这种机制可能解释了先前在暴露于流动的细胞上观察到的蛋白质图案形成,并可能构成流动感知的初始步骤。