Active matter under control: Insights from response theory.

Luke K. Davis, Karel Proesmans, and Etienne Fodor. Physical Review X (2024)

Highlighted in the Physics magazine as a viewpoint: https://physics.aps.org/articles/v17/20.

Active matter is a class of physical systems where each individual unit constantly converts a given source of energy into sustained dynamics, resulting in collective behavior that is very different from systems at thermal equilibrium. Efficient control of active systems opens the door to machines and materials that can perform novel functions. But their out-of-equilibrium nature presents major difficulties to existing control frameworks that are built for equilibrium systems. Here, we present a systematic optimal control framework that takes into account the out-of-equilibrium nature of active matter.

Our new framework leverages recent developments in stochastic thermodynamics and response theory, coupled with a standard calculus of variations, to build a generic recipe that finds the optimal protocol for driving a continuous-state or discrete-state active system between two different states. The framework requires computing only steady-state averages and response functions, based on correlation functions in the unperturbed state, for which we provide explicit formulas.

We apply our framework to one- and many-body scenarios, revealing a general feature arising from the control of active systems: In contrast to systems at thermal equilibrium, where the protocol achieving the least dissipation is always the slowest one, the optimal protocol has instead a finite duration that achieves the best trade-off between the dissipation stemming from the external perturbation and that coming from internal activity.

Our control framework reveals new insights into the thermodynamics of active systems and lays down a road map for the optimal control of a broad array of active systems, taking one step closer to active-matter technology.

Biophysical basis of phage crystalline droplet-mediated antibiotic tolerance in pathogenic bacteria. Jan Böhning, Miles Graham, Suzanne C. Letham, Luke K. Davis, Ulrich Schulze, Robin A. Corey, Philip J. Stansfeld, Philip Pearce, Abul K. Tarafder, and Tanmay Bharat. Nature Communications (2023)

Inoviruses are filamentous phages infecting numerous prokaryotic phyla. Inoviruses can self-assemble into mesoscale structures with liquid-crystalline order, termed tactoids, which protect bacterial cells in Pseudomonas aeruginosa biofilms from antibiotics. Here, we investigate the structural, biophysical, and protective properties of tactoids formed by the P. aeruginosa phage Pf4 and Escherichia coli phage fd. A cryo-EM structure of the capsid from fd revealed distinct biochemical properties compared to Pf4. Fd and Pf4 formed tactoids with different morphologies that arise from differing phage geometries and packing densities, which in turn gave rise to different tactoid emergent properties. Finally, we showed that tactoids formed by either phage protect rod-shaped bacteria from antibiotic treatment, and that direct association with a tactoid is required for protection, demonstrating the formation of a diffusion barrier by the tactoid. This study provides insights into how filamentous molecules protect bacteria from extraneous substances in biofilms and in host-associated infections.

Crowding-induced phase separation of nuclear transport receptors in an FG nucleoporin assembly. Luke K. Davis, Ian J. Ford, and Bart W. Hoogenboom. eLife (2022)

Editor’s evaluation: This theoretical study describes the interaction of a planar brush or film of the resident unstructured components of the nuclear pore complex (NPC) called nucleoporins (FG-nups) and different nuclear transport receptors (NTRs). The authors describe impacts of competitive binding that give rise to enrichment of the NTRs, NTF2 and importin-β, at different depths of the FG-nup film, which could relate to experimental observations in other studies, as well as evidence that crowding could promote the rate of nuclear transport by modulating FG-NTR binding/unbinding. The conclusions were found to be generally supported by the data, relevant to the field of nuclear transport, and able to make specific predictions that can be experimentally tested in the future.

Physical modelling of multivalent interactions in the nuclear pore complex.

Luke K. Davis, Andela Saric, Bart W. Hoogenboom, and Anton Zilman. Biophys. J. (2021)

In the nuclear pore complex, intrinsically disordered proteins (FG Nups), along with their interactions with more globular proteins called nuclear transport receptors (NTRs), are vital to the selectivity of transport into and out of the cell nucleus. Although such interactions can be modeled at different levels of coarse graining, in vitro experimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, in which the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and noncohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity in a minimal fashion and compare them with experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs does play a role in determining equilibrium binding properties but is of much greater significance when it comes to unbinding and binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.

Modelling fibrillogenesis of collagen-mimetic molecules. Anne E. Hafner, Noemi G. Gyori, Ciaran A. Bench, Luke K. Davis, and Andela Saric. Biophys. J. (2021)

Biophysical Journal Paper of the Year Award (2021) | Made the cover of Volume 119 Number 9 (Nov 3rd 2020). See here for a lay article I wrote about this work.

One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular matrix, where they self-assemble into fibrils of well-defined axial striped patterns. This striped fibrillar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signaling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here, we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril axial pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the striped fibrillar pattern cannot be easily predicted from the interactions between two monomers but is an emergent result of multibody interactions. Our results can help address collagen remodeling in diseases and aging and guide the design of collagen scaffolds for biotechnological applications.

Intrinsically disordered nuclear pore proteins show ideal-polymer morphologies and dynamics.

Luke K. Davis, Ian J. Ford, Andela Saric, and Bart W. Hoogenboom. Phys. Rev. E. (2020)

In the nuclear pore complex, intrinsically disordered nuclear pore proteins (FG Nups) form a selective barrier for transport into and out of the cell nucleus, in a way that remains poorly understood. The collective FG Nup behavior has long been conceptualized either as a polymer brush, dominated by entropic and excluded-volume (repulsive) interactions, or as a hydrogel, dominated by cohesive (attractive) interactions between FG Nups. Here we compare mesoscale computational simulations with a wide range of experimental data to demonstrate that FG Nups are at the crossover point between these two regimes. Specifically, we find that repulsive and attractive interactions are balanced, resulting in morphologies and dynamics that are close to those of ideal polymer chains. We demonstrate that this property of FG Nups yields sufficient cohesion to seal the transport barrier, and yet maintains fast dynamics at the molecular scale, permitting the rapid polymer rearrangements needed for transport events.

A programmable DNA-origami platform for organizing intrinsically disordered nucleoporins.

Patrick D. E. Fisher, Qi Shen, Bernice Akpinar, Luke K. Davis, Kenny Chung, David Baddeley, Andela Saric, Thomas Melia, Bart W. Hoogenboom, C. Patrick Lusk, and Chenxiang Lin. ACS Nano (2018)

Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ∼40 nm diameter transport channel contributes to their collective properties and function. To begin to answer these questions, we have used DNA origami to build a cylinder that mimics the dimensions of the central transport channel and can house a specified number of FG-domains at specific positions with easily tunable design parameters, such as grafting density and topology. We find the overall morphology of the FG-domain assemblies to be dependent on their chemical composition, determined by the type and density of FG-repeat, and on their architectural confinement provided by the DNA cylinder, largely consistent with here presented molecular dynamics simulations based on a coarse-grained polymer model. In addition, high-speed atomic force microscopy reveals local and reversible FG-domain condensation that transiently occludes the lumen of the DNA central channel mimics, suggestive of how the NPC might establish its permeability properties.