Search and Capture Efficiency of Dynamic Microtubules for Centrosome Relocation during IS Formation

Area of Science:

• Cellular Biology
• Immunology
• Biophysics

Background:

• Cytotoxic T lymphocytes (T cells) form an immunological synapse (IS) upon encountering antigen-presenting cells.
• IS formation requires microtubule organizing center (MTOC) repositioning via dynamic microtubules (MTs) to the contact zone.
• The efficiency and mechanism by which MTs locate the IS within the cell remain unclear.

Purpose of the Study:

• To investigate how dynamic microtubules (MTs) search the constrained cellular volume to find the immunological synapse (IS).
• To model the binding of MTs to dynein anchored at the IS cortex.
• To determine an optimal search strategy for MTs to efficiently reach the IS.

Main Methods:

• Development of simple mathematical and numerical models of cellular components involved in IS formation.
• Estimation of search efficiency by calculating the time for MTs to reach the dynein-enriched IS region.
• Quantification of average search time across a range of model parameters.

Main Results:

• Minimal MT search times occur when the IS forms at sites nearest or farthest from the perinuclear MTOC.
• Search time increases with distance from these optimal sites, peaking near the cell's equator.
• Search time is significantly influenced by the number of searching MTs and the MTOC's distance from the nucleus.

Conclusions:

• The spatial positioning of the IS relative to the MTOC critically affects microtubule search efficiency.
• An optimized search strategy exists, favoring extreme positions for rapid MT capture at the IS.
• Understanding MT dynamics in IS formation provides insights into T cell activation and immune response efficacy.