Anisotropic swelling due to hydration constrains anisotropic elasticity in biomaterial fibers.

Naturally occurring protein fibers often undergo anisotropic swelling when hydrated. Within a tendon, a hydrated collagen fibril's radius expands by 40% but its length only increases by 5%. The same effect, with a similar relative magnitude, is observed for single hair shafts.

Dynamical Network Stability Analysis of Multiple Biological Ages Provides a Framework for Understanding the Aging Process.

Widespread interest in nondestructive biomarkers of aging has led to a multitude of biological ages that each proffers a "true" health-adjusted individual age. Although each measure provides salient information on the aging process, they are each univariate, in contrast to the "hallmark" and "pillar" theories of aging, which are explicitly multidimensional, multicausal, and multiscale. Fortunately, multiple biological ages can be systematically combined into a multidimensional network representation.

Network dynamical stability analysis reveals key "mallostatic" natural variables that erode homeostasis and drive age-related decline of health.

Using longitudinal study data, we dynamically model how aging affects homeostasis in both mice and humans. We operationalize homeostasis as a multivariate mean-reverting stochastic process. We hypothesize that biomarkers have stable equilibrium values, but that deviations from equilibrium of each biomarker affects other biomarkers through an interaction network-this precludes univariate analysis.

Network dynamical stability analysis reveals key "mallostatic" natural variables that erode homeostasis and drive age-related decline of health.

Using longitudinal study data, we dynamically model how aging affects homeostasis in both mice and humans. We operationalize homeostasis as a multivariate mean-reverting stochastic process. We hypothesize that biomarkers have stable equilibrium values, but that deviations from equilibrium of each biomarker affects other biomarkers through an interaction network - this precludes univariate analysis.

Modelling lifespan reduction in an exogenous damage model of generic disease.

We model the effects of disease and other exogenous damage during human aging. Even when the exogenous damage is repaired at the end of acute disease, propagated secondary damage remains. We consider both short-term mortality effects due to (acute) exogenous damage and long-term mortality effects due to propagated damage within the context of a generic network model (GNM) of individual aging that simulates a U.

Torsion and bistability of double-twist elastomers.

We investigate the elastic properties of anisotropic elastomers with a double-twist director field, which is a model for collagen fibrils or blue phases. We observe a significant Poynting-like effect, coupling torsion (fibril twist) and extension. For freely-rotating boundary conditions, we identify a structural bistability at very small extensional strains which undergoes a saddle-node bifurcation at a critical strain - at approximately 1% strain for a parameterization appropriate for collagen fibrils.

Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions.

As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robustness and resilience, which respectively represent resisting or recovering from damage.

Interpretable machine learning for high-dimensional trajectories of aging health.

We have built a computational model for individual aging trajectories of health and survival, which contains physical, functional, and biological variables, and is conditioned on demographic, lifestyle, and medical background information. We combine techniques of modern machine learning with an interpretable interaction network, where health variables are coupled by explicit pair-wise interactions within a stochastic dynamical system. Our dynamic joint interpretable network (DJIN) model is scalable to large longitudinal data sets, is predictive of individual high-dimensional health trajectories and survival from baseline health states, and infers an interpretable network of directed interactions between the health variables.

Non-Fickian single-file pore transport.

Single-file diffusion exhibits anomalously slow collective transport when particles are able to immobilize by binding and unbinding to the one-dimensional channel within which the particles diffuse. We have explored this system for short porelike channels using a symmetric exclusion process with fully stochastic dynamics. We find that for shorter channels, a non-Fickian regime emerges for slow binding kinetics.

D-band strain underestimates fibril strain for twisted collagen fibrils at low strains.

Collagen fibrils are the main structural component of load-bearing tissues such as tendons, ligaments, skin, the cornea of the eye, and the heart. The D-band of collagen fibrils is an axial periodic density modulation that can be easily characterized by tissue-level X-ray scattering. During mechanical testing, D-band strain is often used as a proxy for fibril strain.

The degree of frailty as a translational measure of health in aging.

Frailty is a multiply determined, age-related state of increased risk for adverse health outcomes. We review how the degree of frailty conditions the development of late-life diseases and modifies their expression. The risks for frailty range from subcellular damage to social determinants.

Chiral phase-coexistence in compressed double-twist elastomers.

We adapt the theory of anisotropic rubber elasticity to model cross-linked double-twist liquid crystal cylinders such as exhibited in biological systems. In mechanical extension we recover strain-straightening, but with an exact expression in the small twist-angle limit. In compression, we observe coexistence between high and low twist phases.

Non-equilibrium growth and twist of cross-linked collagen fibrils.

The lysyl oxidase (LOX) enzyme that catalyses cross-link formation during the assembly of collagen fibrils in vivo is too large to diffuse within assembled fibrils, and so is incompatible with a fully equilibrium mechanism for fibril formation. We propose that enzymatic cross-links are formed at the fibril surface during the growth of collagen fibrils; as a consequence no significant reorientation of previously cross-linked collagen molecules occurs inside collagen fibrils during fibril growth in vivo. By imposing local equilibrium only at the fibril surface, we develop a coarse-grained quantitative model of in vivo fibril structure that incorporates a double-twist orientation of collagen molecules and a periodic D-band density modulation along the fibril axis.

Bayesian counting of photobleaching steps with physical priors.

Counting fluorescence photobleaching steps is commonly used to infer the number n of monomeric units of individual oligomeric protein complexes or misfolded protein aggregates. We present a principled Bayesian approach for counting that incorporates the statistics of photobleaching. Our physics-based prior leads to a simple and efficient numerical scheme for maximum a posteriori probability (MAP) estimates of the initial fluorophore number n^.

Anomalously slow transport in single-file diffusion with slow binding kinetics.

We computationally study the effects of binding kinetics to the channel wall, leading to transient immobility, on the diffusive transport of particles within narrow channels, that exhibit single-file diffusion (SFD). We find that slow binding kinetics leads to an anomalously slow diffusive transport. Remarkably, the scaled diffusivity D[over ̂] characterizing transport exhibits scaling collapse with respect to the occupation fraction p of sites along the channel.

Polymorphism of stable collagen fibrils.

Collagen fibrils are versatile self-assembled structures that provide mechanical integrity within mammalian tissues. The radius of collagen fibrils vary widely depending on experimental conditions in vitro or anatomical location in vivo. Here we explore the variety of thermodynamically stable fibril configurations that are available.

Photobleaching of randomly rotating fluorescently decorated particles.

Randomly rotating particles that have been isotropically labeled with rigidly linked fluorophores will undergo non-isotropic (patchy) photobleaching under illumination due to the dipole coupling of fluorophores with light. For a rotational diffusion rate D of the particle and a photobleaching time scale τ of the fluorophores, the dynamics of this process are characterized by the dimensionless combination Dτ. We find significant interparticle fluctuations at intermediate Dτ.

Unifying aging and frailty through complex dynamical networks.

To explore the mechanistic relationships between aging, frailty and mortality, we developed a computational model in which possible health attributes are represented by the nodes of a complex network, with the connections showing a scale-free distribution. Each node can be either damaged (i.e.

Network model of human aging: Frailty limits and information measures.

Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f≤1.

αTAT1 controls longitudinal spreading of acetylation marks from open microtubules extremities.

Acetylation of the lysine 40 of α-tubulin (K40) is a post-translational modification occurring in the lumen of microtubules (MTs) and is controlled by the α-tubulin acetyl-transferase αTAT1. How αTAT1 accesses the lumen and acetylates α-tubulin there has been an open question. Here, we report that acetylation starts at open ends of MTs and progressively spreads longitudinally from there.

Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils.

Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development.

Dynamical network model for age-related health deficits and mortality.

How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging.

Single file diffusion into a semi-infinite tube.

We investigate single file diffusion (SFD) of large particles entering a semi-infinite tube, such as luminal diffusion of proteins into microtubules or flagella. While single-file effects have no impact on the evolution of particle density, we report significant single-file effects for individually tracked tracer particle motion. Both exact and approximate ordering statistics of particles entering semi-infinite tubes agree well with our stochastic simulations.

Cluster coarsening on drops exhibits strong and sudden size-selectivity.

Autophagy, an important process for degradation of cellular components, requires the targeting of autophagy receptor proteins to potential substrates. Receptor proteins have been observed to form clusters on membranes. To understand how receptor clusters might affect autophagy selectivity, we model cluster coarsening on a polydisperse collection of spherical drop-like substrates.