Search and capture efficiency of dynamic microtubules for centrosome relocation during IS formation

Abstract

Upon contact with antigen presenting cells (APCs) cytotoxic T lymphocytes (T cells) establish a highly organized contact zone denoted as immunological synapse (IS). The formation of the IS implies relocation of the microtubule organizing center (MTOC) towards the contact zone, which necessitates a proper connection between MTOC and IS via dynamic microtubules (MTs). The efficiency of the MTs finding the IS within relevant time scale is, however, still illusive. We investigate how MTs search the three-dimensional constrained cellular volume for the IS and bind upon encounter to dynein anchored at the IS cortex. The search efficiency is estimated by calculating the time required for the MTs to reach the dynein-enriched region of the IS. In this study, we develop simple mathematical and numerical models incorporating relevant components of a cell and propose an optimal search strategy. Using the mathematical model, we have quantified the average search time for a wide range of model parameters and proposed an optimized set of values leading to the minimum capture time. Our results show that search times are minimal when the IS formed at the nearest or at the farthest sites on the cell surface, with respect to the perinuclear MTOC. The search time increases monotonically away from these two specific sites and are maximal at an intermediate position near the equator of the cell. We observed that search time strongly depends on the number of searching MTs and distance of the MTOC from the nuclear surface.Comment: 35 pages, 9 Figures, and 2 Table