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Ryan J. McGorty

Publications and source records attributed to Ryan J. McGorty.

5 recordsLinked to original sources

BARCODE: Biomaterial Activity Readouts to Categorize, Optimize, Design and Engineer for high throughput screening and characterization of dynamically restructuring soft materials

Active, responsive, nonequilibrium materials, at the forefront of materials engineering, offer dynamical restructuring, mobility and other complex life-like properties. Yet, this enhanced functionality comes with significant amplification of the size and complexity of the datasets needed to characterize their properties, thereby challenging conventional approaches to analysis. To meet this need, we present BARCODE (Biomaterial Activity Readouts to Categorize, Optimize, Design and Engineer), an open-access software that automates high throughput screening of microscopy video data to enable nonequilibrium material optimization and discovery. BARCODE produces a unique fingerprint or barcode of performance metrics that visually and quantitatively encodes dynamic material properties with minimal file size. Using three complementary material agnostic analysis branches, BARCODE significantly reduces data dimensionality and size, while providing rich, multiparametric outputs and rapid tractable characterization of activity and structure. We analyze a series of datasets of cytoskeleton networks and cell monolayers to demonstrate the ability of BARCODE to accelerate and streamline screening and analysis, reveal unexpected correlations and emergence, and enable broad non-expert data access, comparison, and sharing.

cond-mat.soft↗

Motor antagonism dictates emergent dynamics in active double networks tuned by crosslinkers

The cytoskeleton relies on diverse populations of motors, filaments, and binding proteins acting in concert to enable non-equilibrium processes ranging from mitosis to chemotaxis. Its versatile reconfigurability, programmed by interactions between its constituents, make the cytoskeleton foundational active matter. Yet, current active matter endeavors are limited largely to single force-generating components acting on a single substrate, far from the composite cytoskeleton in cells. Here, we engineer actin-microtubule double-networks, driven by kinesin and myosin motors and tuned by crosslinkers, to ballistically restructure and flow with speeds that span three orders of magnitude depending on the composite formulation and time relative to the onset of motor activity. Differential dynamic microscopy analyses reveal that kinesin and myosin compete to delay the onset of acceleration and suppress discrete restructuring events, while passive crosslinking of either actin or microtubules has an opposite effect. Our minimal advection-diffusion model and spatial correlation analyses correlate these dynamics to structure, with motor antagonism suppressing reconfiguration and de-mixing, while crosslinking enhances clustering. Despite the rich formulation space and emergent formulation-dependent structures, the non-equilibrium dynamics across all networks and timescales can be organized into three classes: slow isotropic reorientation, fast directional flow, and multimode restructuring. Moreover, our mathematical model demonstrates that diverse structural motifs can arise simply from the interplay between motor-driven advection and frictional drag. These general features of our platform facilitate applicability to other active matter systems, and shed light on diverse ways that cytoskeletal components can cooperate or compete to enable wide-ranging cellular processes.

physics.bio-ph↗

Cooperative rheological state-switching of enzymatically-driven composites of circular DNA and dextran

Polymer topology, which plays a principal role in the rheology of polymeric fluids, and non-equilibrium materials, which exhibit time-varying rheological properties, are topics of intense investigation. Here, we push composites of circular DNA and dextran out-of-equilibrium via enzymatic digestion of DNA rings to linear fragments. Our time-resolved rheology measurements reveal discrete state-switching, with composites undergoing abrupt transitions between dissipative and elastic-like states. The gating time and lifetime of the elastic-like states, and the magnitude and sharpness of the transitions, are surprisingly decorrelated from digestion rates and non-monotonically depend on the DNA fraction. We model our results using sigmoidal two-state functions to show that bulk state-switching can arise from continuous molecular-level activity due to the necessity for cooperative percolation of entanglements to support macroscopic stresses. Our platform, coupling the tunability of topological composites with the power of enzymatic reactions, may be leveraged for diverse material applications from wound-healing to self-repairing infrastructure.

cond-mat.soft↗

Active Cytoskeletal Composites Display Emergent Tunable Contractility and Restructuring

The cytoskeleton is a model active matter system that controls diverse cellular processes from division to motility. While both active actomyosin dynamics and actin-microtubule interactions are key to the cytoskeleton's versatility and adaptability, an understanding of their interplay is lacking. Here, we couple microscale experiments with mechanistic modeling to elucidate how connectivity, rigidity, and force-generation affect emergent material properties in in vitro composites of actin, tubulin, and myosin. We use time-resolved differential dynamic microscopy and spatial image autocorrelation to show that ballistic contraction occurs in composites with sufficient flexibility and motor density, but that a critical fraction of microtubules is necessary to sustain controlled dynamics. Our active double-network models reveal that percolated actomyosin networks are essential for contraction, but that networks with comparable actin and microtubule densities can uniquely resist mechanical stresses while simultaneously supporting substantial restructuring. Our findings provide a much-needed blueprint for designing cytoskeleton-inspired materials that couple tunability with resilience and adaptability.

cond-mat.soft↗

Topology-dependent anomalous dynamics of ring and linear DNA are sensitive to cytoskeleton crosslinking

Cytoskeletal crowding plays a key role in the diffusion of DNA molecules through the cell, acting as a barrier to effective intracellular transport and conformational stability required for such processes as transfection, viral infection, and gene therapy. Here we elucidate the transport properties and conformational dynamics of linear and ring DNA molecules diffusing through entangled and crosslinked composite networks of actin and microtubules. We couple single-molecule conformational tracking with differential dynamic microscopy to reveal that ring and linear DNA exhibit surprisingly distinct transport properties that are influenced differently by cytoskeleton crosslinking. Ring DNA coils are swollen and undergo heterogeneous and biphasic subdiffusion that is hindered by crosslinking. Conversely, crosslinking actually facilitates the single-mode subdiffusion that compacted linear chains exhibit. Our collective results demonstrate that transient threading by cytoskeleton filaments plays a key role in the dynamics of ring DNA, whereas the mobility of the cytoskeleton dictates transport of linear DNA.

cond-mat.soft↗