Biology subjects

GrandPre, T.

Publications and source records attributed to GrandPre, T..

5 recordsLinked to original sources

bioRxiv2024

Membrane wetting by biomolecular condensates is facilitated by mobile tethers

Biomolecular condensates frequently rely on membrane interactions for recruitment, localization, and biochemical substrates. Many of these interactions are mediated by membrane-anchored molecules such as proteins or specific lipids, which we refer to as "mobile tethers" since they can typically diffuse within the membrane while still interacting with the condensate. The presence of mobile tethers creates a surface with dynamic and spatially inhomogeneous wetting properties that are typically overlooked by traditional wetting theories. Here, we propose a general theoretical framework to study how mobile tethers impact both equilibrium and dynamic properties of condensate wetting. We show that a favorable tether-condensate interaction leads to tether enrichment at the condensate-membrane interface, which modifies the equilibrium surface tension and contact angle. Increasing tether abundance on the membrane can drive transitions between wetting regimes, with only a modest tether density and binding energy required for biologically relevant scenarios. Furthermore, tethers modulate how condensates react to complex membrane geometries. By helping condensates coat membranes, mobile tethers can facilitate condensate localization to junctions of membrane structures, such as the reticulated membranes inside the algal pyrenoid. Both tether abundance and mobility affect how droplets interact with complex membrane geometries, such as droplet migration along membrane tubules of varying radii. These results provide a framework to study the implications of tether-mediated condensate-membrane interactions for cellular organization and function.

biophysics↗

bioRxiv2024

Trait-space patterning is dictated by the tempo and mode of mutation

In large, natural ecosystems, many ({gtrsim} 1) phenotypically relevant mutants can emerge over the characteristic turnover time of the population. When this is the case, there can be eco-evolutionary feedback between the dynamical processes that underlie mutation, selection and ecology. In this paper, we show that, owing to such feedback, the precise details of the mutational process can have a qualitative impact on the long-term behavior of an eco-evolutionary system, in contrast to the classical population genetic assumption that all mutations can be modeled with an effective, homogeneous rate. We demonstrate this in the context of a version of MacArthurs consumer-resource model in which consumers mutate along a resource preference trait-space. Starting from a stochastic individual-based model, we simulate the system in the case where mutations are exogenously generated at a fixed rate (e.g. via external mutagens) and in the case where mutations are coupled to replication (e.g. via DNA copying errors). We find that, surprisingly, replication-coupled mutations are capable of generating a patterned phase in the limit of fast ecological relaxation - precisely the regime where classical population genetic models are expected to operate. We derive the appropriate mean-field description of the stochastic model and use it to show that the patterned phase comes about due to a Turing-like mechanism driven by the non-reciprocal and nonlinear nature of replicative mutations. We demonstrate that these results are robust to demographic noise and model choices and we discuss systems in which this phenomenology might be relevant.

evolutionary biology↗

bioRxiv2023

Effects of linker length on phase separation: lessons from the Rubisco-EPYC1 system of the algal pyrenoid

Biomolecular condensates are membraneless organelles formed via phase separation of macromolecules, typically consisting of bond-forming "stickers" connected by flexible "linkers". Linkers have diverse roles, such as occupying space and facilitating interactions. To understand how linker length relative to other lengths affects condensation, we focus on the pyrenoid, which enhances photosynthesis in green algae. Specifically, we apply coarse-grained simulations and analytical theory to the pyrenoid proteins of Chlamydomonas reinhardtii: the rigid holoenzyme Rubisco and its flexible partner EPYC1. Remarkably, halving EPYC1 linker lengths decreases critical concentrations by ten-fold. We attribute this difference to the molecular "fit" between EPYC1 and Rubisco. Varying Rubisco sticker locations reveals that the native sites yield the poorest fit, thus optimizing phase separation. Surprisingly, shorter linkers mediate a transition to a gas of rods as Rubisco stickers approach the poles. These findings illustrate how intrinsically disordered proteins affect phase separation through the interplay of molecular length scales.

biophysics↗

bioRxiv2022

Phase-separating pyrenoid proteins form complexes in the dilute phase

While most studies of biomolecular phase separation have focused on the condensed phase, relatively little is known about the dilute phase. Theory suggests that stable complexes form in the dilute phase of two-component phase-separating systems, impacting phase separation; however, these complexes have not been interrogated experimentally. We show that such complexes indeed exist, using an in vitro reconstitution system of a phase-separated organelle, the algal pyrenoid, consisting of purified proteins Rubisco and EPYC1. Applying fluorescence correlation spectroscopy (FCS) to measure diffusion coefficients, we found that complexes form in the dilute phase with or without condensates present. The majority of these complexes contain exactly one Rubisco molecule. Additionally, we developed a simple analytical model which recapitulates experimental findings and provides molecular insights into the dilute phase organization. Thus, our results demonstrate the existence of protein complexes in the dilute phase, which could play a significant role in the stability, dynamics, and regulation of condensates.

biophysics↗

bioRxiv2021

Kinetic frustration by limited bond availability controls the LAT protein condensation phase transition on membranes

LAT is a membrane-linked scaffold protein that undergoes a phase transition to form a two-dimensional protein condensate on the membrane during T cell activation. Governed by tyrosine phosphorylation, LAT recruits various proteins that ultimately enable condensation through a percolation network of discrete and selective protein-protein interactions. Here we describe detailed kinetic measurements of the phase transition, along with coarse-grained model simulations, that reveal LAT condensation is kinetically frustrated by the availability of bonds to form the network. Unlike typical miscibility transitions in which compact domains may coexist at equilibrium, the LAT condensates are dynamically arrested in extended states, kinetically trapped out of equilibrium. Modeling identifies the structural basis for this kinetic arrest as the formation of spindle arrangements, favored by limited multivalent binding interactions along the flexible, intrinsically disordered LAT protein. These results reveal how local factors controlling the kinetics of LAT condensation enable formation of different, stable condensates, which may ultimately coexist within the cell.

biophysics↗