Forcing it on: Cytoskeletal dynamics during lymphocyte activation

Forcing it on: Cytoskeletal dynamics during lymphocyte activation

Activation of T lymphocytes by antigen-presenting cells involves cell spreading driven by large-scale physical rearrangements of the actin cytoskeleton and the cell membrane, and accompanied by the assembly of signaling molecules into dynamic microclusters. Several recent observations suggest that mechanical forces are important for efficient T cell activation. How forces arise from the dynamics of the cytoskeleton and the membrane during contact formation, and their effect on microcluster assembly and signaling activation is not well understood. We imaged the membrane topography, actin dynamics...

Date

October 23, 2012 - 11:00am

Location

IBB Room 1128

Activation of T lymphocytes by antigen-presenting cells involves cell spreading driven by large-scale physical rearrangements of the actin cytoskeleton and the cell membrane, and accompanied by the assembly of signaling molecules into dynamic microclusters. Several recent observations suggest that mechanical forces are important for efficient T cell activation. How forces arise from the dynamics of the cytoskeleton and the membrane during contact formation, and their effect on microcluster assembly and signaling activation is not well understood. We imaged the membrane topography, actin dynamics and the spatiotemporal localization of signaling clusters during the very early stages of spreading. We found that the formation of signaling clusters was closely correlated with the movement and topography of the membrane in contact with the activating surface. Further, we observed membrane waves driven by actin polymerization originating at these signaling clusters. These actin-driven membrane protrusions likely play an important role in force generation at the immune synapse. In order to study the role of cytoskeletal forces during T-cell activation, we studied cell spreading on elastic substrates to measure cellular forces during spreading. We found that substrate stiffness influences cell morphology, actin dynamics and cellular traction forces. Efforts to determine the quantitative relationships between cellular forces and signaling are underway. Our results suggest a role for cytoskeleton driven forces during signaling activation in lymphocytes.