Line Tension and Stability of Domains in Cell-Adhesion Zones Mediated by Long and Short Receptor-Ligand Complexes

Submicron scale domains of membrane-anchored receptors play an important role in cell signaling. Central questions concern the stability of these microdomains, and the mechanisms leading to the domain formation. In immune-cell adhesion zones, microdomains of short receptor-ligand complexes form next to domains of significantly longer receptor-ligand complexes. The length mismatch between the receptor-ligand complexes leads to membrane deformations and has been suggested as a possible cause of the domain formation. The domain formation is a nucleation and growth process that depends on the line tension and free energy of the domains. Using a combination of analytical calculations and Monte Carlo simulations, we derive here general expressions for the line tension between domains of long and short receptor-ligand complexes and for the adhesion free energy of the domains. We argue that the length mismatch of receptor-ligand complexes alone is sufficient to drive the domain formation, and obtain submicron-scale minimum sizes for stable domains that are consistent with the domain sizes observed during immune-cell adhesion.

膜锚定受体的亚微米尺度结构域在细胞信号转导中发挥重要作用。当前的核心科学问题聚焦于这些微结构域的稳定性，以及其形成的潜在机制。在免疫细胞黏附区域中，短受体-配体复合物的微结构域会与长程受体-配体复合物的结构域毗邻形成。受体-配体复合物间的长度错配会引发膜形变，该现象被认为是结构域形成的潜在诱因之一。结构域的形成属于成核与生长过程，其依赖于结构域的线张力与自由能。本研究结合解析计算与蒙特卡洛（Monte Carlo）模拟方法，推导出了长短受体-配体复合物结构域间的线张力，以及结构域黏附自由能的通用表达式。本研究论证了仅靠受体-配体复合物的长度错配即可驱动结构域形成，并得到了稳定结构域的亚微米尺度最小尺寸，该结果与免疫细胞黏附过程中观测到的结构域尺寸相符。