Biology subjects

Palaia, I.

Publications and source records attributed to Palaia, I..

7 recordsLinked to original sources

bioRxiv2024

Charge distribution of coating brush drives inter-chromosome attraction

The condensation of charged polymers is an important driver for the formation of biomolecular condensates. Recent experiments suggest that this mechanism also controls the clustering of eukaryotic chromosomes during the late stages of cell division. In this process, inter-chromosome attraction is driven by the condensation of cytoplasmic RNA and Ki-67, a charged intrinsically disordered protein that coats the chromosomes as a brush. Attraction between chromosomes has been shown to be specifically promoted by a localized charged patch on Ki-67, although the physical mechanism remains unclear. To elucidate this process, we combine here coarse-grained simulations and analytical theory to study the RNA-mediated interaction between charged polymer brushes on the chromosome surfaces. We show that the charged patch on Ki-67 leads to inter-chromosome attraction via RNA bridging between the two brushes, whereby the RNA preferentially interacts with the charged patches, leading to stable, long-range forces. By contrast, if the brush is uniformly charged, bridging is basically absent due to complete adsorption of RNA onto the brush. Moreover, the RNA dynamics becomes caged in presence of the charged patch, while remaining diffusive with uniform charge. Our work sheds light on the physical origin of chromosome clustering, while also suggesting a general mechanism for cells to tune work production by biomolecular condensates via different charge distributions.

biophysics↗

bioRxiv2024

Caging of membrane-to-cortex attachment proteins can trigger cellular symmetry breaking

To migrate, divide, and change shape, cells must regulate the mechanics of their periphery. The cell surface is a complex structure that consists of a thin, contractile cortical actin network tethered to the plasma membrane by specialized membrane-to-cortex attachment (MCA) proteins. This active and constantly fluctuating system maintains a delicate mechanochemical state which permits spontaneous polarization and shape change when needed. Combining in silico, in vitro, and in vivo experiments we show how membrane viscosity and MCA protein length regulate cortical dynamics. We reveal a novel mechanism whereby caging of linker proteins in the actin cortex allows for the amplification of small changes in these key parameters, leading to major alterations of cortical contractility. In cells, this mechanism alone gives rise to symmetry breaking phenomena, suggesting that local changes in lipid composition, in combination with the choice of MCA proteins, contribute to the regulation of cellular morphogenesis and function.

biophysics↗

bioRxiv2024

Non-equilibrium remodelling of collagen-IV networks in silico

Collagen IV is one of the main components of the basement membrane, a layer of material that lines the majority of tissues in multicellular organisms. Collagen-IV molecules assemble into networks, providing stiffness and elasticity to tissues and informing cell and organ shape, especially during development. In this work, we develop two coarse grained models for collagen-IV molecules that retain biochemical bond specificity and coarse-grain at different length scales. Through molecular dynamics simulations, we test the assembly and mechanics of the resulting networks and measure their response to strain in terms of stress, microscopic alignment, and bond dynamics. Within the basement membrane, collagen-IV networks rearrange by molecule turnover, which affects tissue organisation and can be linked with enzyme activity. Here we explore network rearrangements via bond remodelling -- the process of dynamical breaking and remaking of bonds between network molecules. We then investigate the effects of active (enzymatic) bond remodelling. We find that this non-equilibrium remodelling allows a network to keep its integrity under strain, while relaxing fully over a variety of timescales - a dynamic response that is unavailable to networks undergoing equilibrium remodelling.

biophysics↗

bioRxiv2022

Mechanochemical rules for membrane-reshaping composite filaments

The sequential exchange of filament composition to increase filament curvature was proposed as a mechanism for how ESCRT-III polymers deform and cut membranes. The relationship between the filament composition and its mechanical effect is lacking. We develop a kinetic model for the assembly of composite filaments that includes protein-membrane adhesion, filament mechanics and membrane mechanics. We identify the physical conditions for such a membrane remodelling and show this mechanism is efficient because sequential polymer assembly lowers the energetic barrier for membrane deformation.

biophysics↗

bioRxiv2022

Controlling cluster size in 2D phase-separating binary mixtures with specific interactions

By varying the concentration of molecules in the cytoplasm or on the membrane, cells can induce the formation of condensates and liquid droplets through phase separation. Their thermodynamics, much studied, depends on the mutual interactions between microscopic constituents. Here, we focus on the kinetics and size control of 2D clusters, forming on membranes. Using molecular dynamics of patchy colloids, we model a system of two species of proteins, giving origin to specific heterotypic bonds. We find that concentrations, together with valence and bond strength, control both the size and the growth time rate of the clusters. In particular, if one species is in large excess, it gradually saturates the binding sites of the other species: the system becomes then kinetically arrested and cluster coarsening slows down or stops, thus yielding effective size selection. This phenomenology is observed both in solid and fluid clusters, which feature additional generic homotypic interactions and are reminiscent of the ones observed on biological membranes.

biophysics↗

bioRxiv2021

Durotaxis of passive nanoparticles on elastic membranes

The transport of macromolecules and nanoscopic particles to a target cellular site is a crucial aspect in many physiological processes. This directional motion is generally controlled via active mechanical and chemical processes. Here we show, by means of molecular dynamics simulations and an analytical theory, that completely passive nanoparticles can exhibit directional motion when embedded in non-uniform mechanical environments. Specifically, we study the motion of a passive nanoparticle adhering to a mechanically non-uniform elastic membrane. We observe a non-monotonic affinity of the particle to the membrane as a function of the membranes rigidity, which results in the particle transport. This transport can be both up or down the rigidity gradient, depending on the absolute values of the rigidities that the gradient spans across. We conclude that rigidity gradients can be used to direct average motion of passive macromolecules and nanoparticles on deformable membranes, resulting in the preferential accumulation of the macromolecules in regions of certain mechanical properties.

biophysics↗

bioRxiv2020

PLCγ1 promotes phase separation of the T cell signaling clusters

SummaryThe T cell receptor (TCR) pathway receives, processes, and amplifies the signal from pathogenic antigens to the activation of T cells. Although major components in this pathway have been identified, the knowledge on how individual components cooperate to effectively transduce signals remains limited. Phase separation emerges as a biophysical principle in organizing signaling molecules into liquid-like condensates. Here we report that phospholipase PLCγ1 promotes phase separation of LAT, a key adaptor protein in the TCR pathway. PLCγ1 directly crosslinks LAT through its two SH2 domains. PLCγ1 also protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK and SLP76 activation. Intriguingly, a non-monotonic effect of PLCγ1 on LAT clustering was discovered. Computer simulations, based on patchy particles, revealed how the cluster size is regulated by protein compositions. Together, these results define a critical function of PLCγ1 in promoting phase separation of the LAT complex and TCR signal transduction.View Full Text

cell biology↗