Under pressure: Hydrogel swelling in a granular medium.

Hydrogels hold promise in agriculture as reservoirs of water in dry soil, potentially alleviating the burden of irrigation. However, confinement in soil can markedly reduce the ability of hydrogels to absorb water and swell, limiting their widespread adoption. Unfortunately, the underlying reason remains unknown. By directly visualizing the swelling of hydrogels confined in three-dimensional granular media, we demonstrate that the extent of hydrogel swelling is determined by the competition between the force exerted by the hydrogel due to osmotic swelling and the confining force transmitted by the surrounding grains. Furthermore, the medium can itself be restructured by hydrogel swelling, as set by the balance between the osmotic swelling force, the confining force, and intergrain friction. Together, our results provide quantitative principles to predict how hydrogels behave in confinement, potentially improving their use in agriculture as well as informing other applications such as oil recovery, construction, mechanobiology, and filtration.

Crack formation and self-closing in shrinkable, granular packings.

Many clays, soils, biological tissues, foods, and coatings are shrinkable, granular materials: they are composed of packed, hydrated grains that shrink when dried. In many cases, these packings crack during drying, critically hindering applications. However, while cracking has been widely studied for bulk gels and packings of non-shrinkable grains, little is known about how packings of shrinkable grains crack. Here, we elucidate how grain shrinkage alters cracking during drying. Using experiments with model shrinkable hydrogel beads, we show that differential shrinkage can dramatically alter crack evolution during drying-in some cases, even causing cracks to spontaneously "self-close". In other cases, packings shrink without cracking or crack irreversibly. We developed both granular and continuum models to quantify the interplay between grain shrinkage, poromechanics, packing size, drying rate, capillarity, and substrate friction on cracking. Guided by the theory, we also found that cracking can be completely altered by varying the spatial profile of drying. Our work elucidates the rich physics underlying cracking in shrinkable, granular packings, and yields new strategies for controlling crack evolution.

Cooperative size sorting of deformable particles in porous media.

Diverse applications-ranging from enhanced oil recovery, filtration, and lab on a chip sorting-rely on the flow-induced transport of deformable particles in porous media. However, how fluid flow can force such particles to squeeze through pore constrictions of complex geometries is poorly understood. Here, we study the transport of model deformable particles in millifluidic porous media with constrictions of tunable aspect ratio. We find that multiple particles can unexpectedly squeeze through large-aspect ratio constrictions, even when isolated particles cannot. This phenomenon arises from pairwise flow-mediated interactions between the particles: when one particle is trapped at a constriction, the increased fluid flow around it enables a second to squeeze past due to locally increased hydrodynamic stresses. This cooperative mechanism causes the particles to ultimately sort themselves by size through the pore space. By revealing a new mode of deformable particle transport in porous media, our work helps to inform real-world applications and provides a straightforward way to sort particles based on size.

Suppressing viscous fingering in structured porous media.

Finger-like protrusions that form along fluid-fluid displacement fronts in porous media are often excited by hydrodynamic instability when low-viscosity fluids displace high-viscosity resident fluids. Such interfacial instabilities are undesirable in many natural and engineered displacement processes. We report a phenomenon whereby gradual and monotonic variation of pore sizes along the front path suppresses viscous fingering during immiscible displacement, that seemingly contradicts conventional expectation of enhanced instability with pore size variability. Experiments and pore-scale numerical simulations were combined with an analytical model for the characteristics of displacement front morphology as a function of the pore size gradient. Our results suggest that the gradual reduction of pore sizes act to restrain viscous fingering for a predictable range of flow conditions (as anticipated by gradient percolation theory). The study provides insights into ways for suppressing unwanted interfacial instabilities in porous media, and provides design principles for new engineered porous media such as exchange columns, fabric, paper, and membranes with respect to their desired immiscible displacement behavior.

Transportable, Chemical Genetic Methodology for the Small Molecule-Mediated Inhibition of Heat Shock Factor 1.

Proteostasis in the cytosol is governed by the heat shock response. The master regulator of the heat shock response, heat shock factor 1 (HSF1), and key chaperones whose levels are HSF1-regulated have emerged as high-profile targets for therapeutic applications ranging from protein misfolding-related disorders to cancer. Nonetheless, a generally applicable methodology to selectively and potently inhibit endogenous HSF1 in a small molecule-dependent manner in disease model systems remains elusive. Also problematic, the administration of even highly selective chaperone inhibitors often has the side effect of activating HSF1 and thereby inducing a compensatory heat shock response. Herein, we report a ligand-regulatable, dominant negative version of HSF1 that addresses these issues. Our approach, which required engineering a new dominant negative HSF1 variant, permits dosable inhibition of endogenous HSF1 with a selective small molecule in cell-based model systems of interest. The methodology allows us to uncouple the pleiotropic effects of chaperone inhibitors and environmental toxins from the concomitantly induced compensatory heat shock response. Integration of our method with techniques to activate HSF1 enables the creation of cell lines in which the cytosolic proteostasis network can be up- or down-regulated by orthogonal small molecules. Selective, small molecule-mediated inhibition of HSF1 has distinctive implications for the proteostasis of both chaperone-dependent globular proteins and aggregation-prone intrinsically disordered proteins. Altogether, this work provides critical methods for continued exploration of the biological roles of HSF1 and the therapeutic potential of heat shock response modulation.