@article {115040, title = {Active emulsions in living cell membranes driven by contractile stresses and transbilayer coupling}, journal = {Proc Natl Acad Sci U S A.}, volume = {119}, year = {2022}, month = {07/2022}, pages = {e2123056119}, abstract = {

The spatiotemporal organization of proteins and lipids on the cell surface has direct functional consequences for signaling, sorting, and endocytosis. Earlier studies have shown that multiple types of membrane proteins, including transmembrane proteins that have cytoplasmic actin binding capacity and lipid-tethered glycosylphosphatidylinositol-anchored proteins (GPI-APs), form nanoscale clusters driven by active contractile flows generated by the actin cortex. To gain insight into the role of lipids in organizing membrane domains in living cells, we study the molecular interactions that promote the actively generated nanoclusters of GPI-APs and transmembrane proteins. This motivates a theoretical description, wherein a combination of active contractile stresses and transbilayer coupling drives the creation of active emulsions, mesoscale liquid order (lo) domains of the GPI-APs and lipids, at temperatures greater than equilibrium lipid phase segregation. To test these ideas, we use spatial imaging of molecular clustering combined with local membrane order, and we demonstrate that mesoscopic domains enriched in nanoclusters of GPI-APs are maintained by cortical actin activity and transbilayer interactions and exhibit significant lipid order, consistent with predictions of the active composite model.

}, doi = {10.1073/pnas.2123056119}, author = {Saha, Suvrajit and Das, A and Patra, C and Anilkumar, AA and Sil, Parijat and Mayor, Satyajit and Rao, Madan} } @article {104421, title = {Active Remodeling of Chromatin and Implications for Folding.}, journal = {J Phys Chem B}, year = {2022}, month = {2021 Dec 24}, abstract = {

Building on the observation that chromatin compaction can be locally modulated by activity, we propose a model of chromatin as an active polymer and study its large scale conformations. In particular, we study an active mechanochemical model of chromosomal folding based on the interplay among polymer elasticity, confinement, topological constraints, and fluctuating active stresses arising from the ATP-dependent action of a variety of chromatin-associated protein machines and chromatin-remodeling proteins and their stochastic turnover. We find that activity drives the chromatin to a nonequilibrium steady state; the statistics of conformations in this nonequilibrium steady state are consistent with recent measurements on intrachromosomal contact probabilities and chromosomal compaction. The contact exponents at steady state show a systematic variation with changes in the nature of activity and the rates of turnover. The steady state configuration of the active chromatin in two dimensions resembles a space-filling Peano curve, which might have implications for the optimization of genome information storage.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.1c08655}, author = {Natesan, Ramakrishnan and Gowrishankar, Kripa and Kuttippurathu, Lakshmi and Kumar, P B Sunil and Rao, Madan} } @article {110442, title = {Active segregation dynamics in the living cell}, journal = {INDIAN JOURNAL OF PHYSICS}, year = {2022}, month = {05/2022}, abstract = {

In this paper, we bring together our efforts in identifying and understanding nonequilibrium phase segregation driven by active processes in the living cell, with special focus on the segregation of cell membrane components driven by active contractile stresses arising from cortical actomyosin. This also has implications for active segregation dynamics in membraneless regions within the cytoplasm and nucleus (3d). We formulate an active version of the Flory-Huggins theory that incorporates a contribution from fluctuating active stresses. Apart from knitting together some of our past theoretical works in a comprehensive narrative, we highlight some new results, and establish a correspondence with recent studies on Active Model B/B+. We point to the many unusual aspects of the dynamics of active phase segregation, such as (i) Anomalous growth dynamics, (ii) Coarsening accompanied by propulsion and coalescence of domains that exhibit non-reciprocal effects, (iii) Segregation into mesoscale domains, (iv) Emergence of a nonequilibrium phase segregated steady state characterised by strong macroscopic fluctuations (fluctuation dominated phase ordering (FDPO)), and (v) Mesoscale segregation even above the equilibrium T-c. Apart from its implications for actively driven segregation of binary fluids, these ideas are at the heart of an Active Emulsion description of the lateral organisation of molecules on the plasma membrane of living cells, whose full molecular elaboration appears elsewhere.

}, doi = {10.1007/s12648-022-02298-z}, author = {Bansal, Ajay and Das, Amit and Rao, Madan} } @article {74438, title = {Active morphogenesis of epithelial monolayers.}, journal = {Phys Rev E}, volume = {100}, year = {2019}, month = {2019 Aug}, pages = {022413}, abstract = {

During typical early-stage embryo development, single-cell-thick tissues of tightly bound epithelial cells autonomously generate profound changes in their shape, forming the basis of organism anatomy. We report on a (covariant) active-hydrodynamic theory of such monolayer morphogenesis that is closed under its shape-changing dynamics-i.e., the degrees of freedom that encode monolayer geometry appear properly as broken-symmetry variables. In our theory, the salient physics of tissue-scale deformations emerges from a balance between the displacement and/or shear of a low-Reynolds-number embedding fluid (the "yolk") and cell-autonomous stresses, themselves a result of combining apical contractile stresses with an elastic-like mechanical response under the constraint of constant cell volume. The leading-order hydrodynamic instabilities include both passive constrained-buckling and active deformation, which can be further categorized by cell shape changes that are either "squamous to columnar" or "regular-prism to truncated-pyramid." The deformations resulting from the latter qualitatively reproduce in vivo observations of the onset of both mesoderm and posterior midgut invaginations, which take place during gastrulation in the model organism Drosophila melanogaster.

}, keywords = {Epithelium, Hydrodynamics, Models, Biological, Morphogenesis, Thermodynamics}, issn = {2470-0053}, doi = {10.1103/PhysRevE.100.022413}, author = {Morris, Richard G and Rao, Madan} } @article {25253, title = {Actomyosin pulsation and flows in an active elastomer with turnover and network remodeling.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Oct 24}, pages = {1121}, abstract = {

Tissue remodeling requires cell shape changes associated with pulsation and flow of the actomyosin cytoskeleton. Here we describe the hydrodynamics of actomyosin as a confined active elastomer with turnover of its components. Our treatment is adapted to describe the diversity of contractile dynamical regimes observed in vivo. When myosin-induced contractile stresses are low, the deformations of the active elastomer are affine and exhibit spontaneous oscillations, propagating waves, contractile collapse and spatiotemporal chaos. We study the nucleation, growth and coalescence of actomyosin-dense regions that, beyond a threshold, spontaneously move as a spatially localized traveling front. Large myosin-induced contractile stresses lead to nonaffine deformations due to enhanced actin and crosslinker turnover. This results in a transient actin network that is constantly remodeling and naturally accommodates intranetwork flows of the actomyosin-dense regions. We verify many predictions of our study in Drosophila embryonic epithelial cells undergoing neighbor exchange during germband extension.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-01130-1}, author = {Banerjee, Deb Sankar and Munjal, Akankshi and Lecuit, Thomas and Rao, Madan} } @article {8348, title = {Active fluidization in dense glassy systems.}, journal = {Soft Matter}, volume = {12}, year = {2016}, month = {2016 Jul 20}, pages = {6268-76}, abstract = {

Dense soft glasses show strong collective caging behavior at sufficiently low temperatures. Using molecular dynamics simulations of a model glass former, we show that the incorporation of activity or self-propulsion, f0, can induce cage breaking and fluidization, resulting in the disappearance of the glassy phase beyond a critical f0. The diffusion coefficient crosses over from being strongly to weakly temperature dependent as f0 is increased. In addition, we demonstrate that activity induces a crossover from a fragile to a strong glass and a tendency of active particles to cluster. Our results are of direct relevance to the collective dynamics of dense active colloidal glasses and to recent experiments on tagged particle diffusion in living cells.

}, issn = {1744-6848}, doi = {10.1039/c5sm02950c}, author = {Mandal, Rituparno and Bhuyan, Pranab Jyoti and Rao, Madan and Dasgupta, Chandan} } @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} }