@article {14978, title = {A DNA-Based T Cell Receptor Reveals a Role for Receptor Clustering in Ligand Discrimination.}, journal = {Cell}, volume = {169}, year = {2017}, month = {2017 Mar 23}, pages = {108-119.e20}, abstract = {

A T\ cell mounts an immune response by measuring the binding strength of its T\ cell receptor (TCR) for peptide-loaded MHCs (pMHC) on an antigen-presenting cell. How T\ cells convert the lifetime of the extracellular TCR-pMHC interaction into an intracellular signal remains unknown. Here, we developed a synthetic signaling system in which the extracellular domains of the TCR and pMHC were replaced with short hybridizing strands of DNA. Remarkably, T\ cells can discriminate between DNA ligands differing by a single base pair. Single-molecule imaging reveals that signaling is initiated when single ligand-bound receptors are converted into clusters, a time-dependent process requiring ligands with longer bound times. A computation model reveals that receptor clustering serves a kinetic proofreading function, enabling ligands with longer bound times to have disproportionally greater signaling outputs. These results suggest that spatial reorganization of receptors plays an important role in ligand discrimination in T\ cell signaling.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2017.03.006}, author = {Taylor, Marcus J and Husain, Kabir and Gartner, Zev J and Mayor, Satyajit and Vale, Ronald D} } @article {14057, title = {Emergent Structures in an Active Polar Fluid: Dynamics of Shape, Scattering, and Merger.}, journal = {Phys Rev Lett}, volume = {118}, year = {2017}, month = {2017 Feb 17}, pages = {078104}, abstract = {

Spatially localized defect structures emerge spontaneously in a hydrodynamic description of an active polar fluid comprising polar "actin" filaments and "myosin" motor proteins that (un)bind to filaments and exert active contractile stresses. These emergent defect structures are characterized by distinct textures and can be either static or mobile-we derive effective equations of motion for these "extended particles" and analyze their shape, kinetics, interactions, and scattering. Depending on the impact parameter and propulsion speed, these active defects undergo elastic scattering or merger. Our results are relevant for the dynamics of actomyosin-dense structures at the cell cortex, reconstituted actomyosin complexes, and 2D active colloidal gels.

}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.118.078104}, author = {Husain, Kabir and Rao, Madan} } @article {3546, title = {Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer.}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, year = {2016}, month = {2016 Mar 22}, pages = {E1645-54}, abstract = {

The surface of a living cell provides a platform for receptor signaling, protein sorting, transport, and endocytosis, whose regulation requires the local control of membrane organization. Previous work has revealed a role for dynamic actomyosin in membrane protein and lipid organization, suggesting that the cell surface behaves as an active composite composed of a fluid bilayer and a thin film of active actomyosin. We reconstitute an analogous system in vitro that consists of a fluid lipid bilayer coupled via membrane-associated actin-binding proteins to dynamic actin filaments and myosin motors. Upon complete consumption of ATP, this system settles into distinct phases of actin organization, namely bundled filaments, linked apolar asters, and a lattice of polar asters. These depend on actin concentration, filament length, and actin/myosin ratio. During formation of the polar aster phase, advection of the self-organizing actomyosin network drives transient clustering of actin-associated membrane components. Regeneration of ATP supports a constitutively remodeling actomyosin state, which in turn drives active fluctuations of coupled membrane components, resembling those observed at the cell surface. In a multicomponent membrane bilayer, this remodeling actomyosin layer contributes to changes in the extent and dynamics of phase-segregating domains. These results show how local membrane composition can be driven by active processes arising from actomyosin, highlighting the fundamental basis of the active composite model of the cell surface, and indicate its relevance to the study of membrane organization.

}, issn = {1091-6490}, doi = {10.1073/pnas.1514030113}, author = {K{\"o}ster, Darius Vasco and Husain, Kabir and Iljazi, Elda and Bhat, Abrar and Bieling, Peter and Mullins, R Dyche and Rao, Madan and Mayor, Satyajit} }