Hanxun Jin

Inherited cardiomyopathies are the leading cause of heart failure in young adults, with limited therapeutic options. Desmin-related cardiomyopathy (DRM), caused by mutations to cytoskeletal proteins and their chaperones, exemplifies this challenge: Here, protein quality control is compromised, leading to toxic protein aggregates that destroy cardiomyocyte contractile machinery. One of the deadliest DRM mutations in the chaperone protein αB crystallin (CRYAB-R120G) lacks a genetically matched preclinical model: Mouse models require massive overexpression of mutant CRYAB, raising questions about physiological relevance. Here, we establish a human model of CRYAB -linked DRM, using induced pluripotent stem cells expressing CRYAB-R120G at near-endogenous levels. We show that three-dimensional mechanical loading, but not fatty acid–based metabolic maturation media, is essential for expressing Desmin, whose aggregation defines DRM. Using microengineered heart tissues, we found that contractile deficits are associated with impaired calcium handling, pointing to electromechanical uncoupling in DRM. Treatment with the Janus kinase 1 inhibitor itacitinib partially rescued contractility, providing a functional validation of this emerging therapeutic strategy.

The podocyte foot process network forms the final barrier of the kidney’s glomerular filtration system. Under mechanical stress this network is prone to injury in which podocytes lose connectivity to their neighbors and begin the progression toward effacement, but what governs its mechanical resilience is unknown. We show that the network is built like a lap joint: two major processes coupled through interdigitating foot processes, a configuration that behaves as a classical shear lag system, with force concentrating at the joint ends and decaying over a characteristic transfer length set by geometry and stiffness. A discrete network model reproduces the continuum shear lag solution and identifies a hierarchy among governing parameters, with cytoskeletal stiffening of the major process amplifying foot process force more potently than basement membrane stiffness. Applying the model to morphometric data from puromycin aminonucleoside nephrosis, a model of human minimal change disease and early focal segmental glomerulosclerosis, reveals a mechanical positive feedback loop: force concentration drives foot process loss, which raises force on surviving segments and accelerates further loss. This nonlinear amplification implies a threshold beyond which failure becomes self-sustaining, analogous to the critical crack length in fracture mechanics.

Recent advances in instrumentation have sparked a transformative journey in materials science, providing insights into the intricate relationship between processing, structure and properties. Among them, cutting-edge in situ micro- and nanoscale mechanical characterization methods, equipped with exceptional spatial and temporal resolution, such as instrumented electron microscopy, X-ray imaging and opto-acoustic techniques, have opened new frontiers in the study of emerging functional and architected materials, including low-dimensional materials, bio-inspired materials and three-dimensional architected metamaterials, underscoring the versatility of these innovative characterization techniques. Furthermore, the integration of artificial intelligence and machine learning offers promising opportunities to streamline high-throughput experimentation processes and enhance the efficiency and accuracy of characterization, and promote the design of next-generation materials. This Review provides a comprehensive overview of the latest micro- and nanoscale mechanical characterization methods. We highlight their interdisciplinary applications to functional and architected materials in the pursuit of solutions for energy, sustainability, semiconductor technology and healthcare.

Hierarchical Mori–Tanaka micromechanics modeling shows that CNC aggregation limits stiffness in SPI nanocomposites, while interphase stiffening from polyDOPA modification improves guides designs toward upper-bound performance.

Photoacoustic imaging (PAI) uniquely combines the advantages of optical contrast with deep tissue penetration capability of acoustic waves, enabling imaging at depths of several centimeters. Conventional PAI methods have relied on pulsed lasers to induce the photoacoustic effect, coupled with arrays of pressure transducers to detect the resulting ultrasound signals. In this work, we propose an alternative all-optical approach that leverages optical deflection to record photoacoustic waves by an array of detection beams. The measured signal is shown to be the Radon transform of the pressure gradients. An optimization-based inversion procedure is used to reconstruct the initial time pressure gradient field. Subsequently, a Galerkin method is used to reconstruct the pressure field from the pressure gradient field. The new modality offers the potential for enhanced sensitivity and reduced signal distortion, advancing the capabilities of PAI beyond traditional transducer-based systems.

Protein quality control (PQC) is essential for maintaining sarcomere integrity in cardiomyocytes. α Crystallin B chain (CRYAB) R120G mutation disrupts CRYAB’s chaperone activity, leading to aggregation of CRYAB and its client proteins (including Desmin), leading to Desmin-related cardiomyopathy (DRM). Prior experimental systems for modeling DRM linked to CRYAB require massive overexpression of CRYAB mutant isoforms, raising questions about translational relevance. Here, we establish the first model of CRYAB-linked DRM that uses genome-edited hiPSC together with isogenic controls, allowing us to study the impact of mutant CRYAB expressed at near endogenous levels. Within micro-engineered heart tissues (μHT), CRYAB-R120G mutant hiPSC-derived cardiomyocytes recapitulated key DRM hallmarks, including Desmin and CRYAB aggregation, contractile dysfunction, and increased vulnerability to PQC pathway inhibition. CRYAB-R120G mutant μHT also exhibited dysfunctional calcium-contraction coupling, which exacerbated contractile deficits at higher pacing frequencies. JAK1 inhibition with Itacitinib partially restored contractile function at higher pacing frequencies, suggesting JAK1 inhibition as a viable therapeutic strategy. By preserving human-specific structural and functional features, our µHT platform enables mechanistic characterization of proteotoxic cardiomyopathies and offers a scalable system for targeted drug screening.

Sustainable alternatives to petroleum‐based plastics are needed urgently, but biodegradable materials from renewable sources often suffer from inadequate mechanical properties. Here, we demonstrate a bio‐inspired strategy to enhance soy protein isolate (SPI) nanocomposites through surface modification of cellulose nanocrystal (CNC) reinforcing filler particles with a polydopamine (polyDOPA) coating via dopamine polymerization under alkaline conditions. This modification creates multifunctional interfaces at filler surfaces that enhance nanocomposite mechanical properties likely by simultaneously altering filler dispersion and filler–matrix interactions. PolyDOPA‐modified CNCs increase the tensile strength and elastic modulus of SPI films (plasticized with 50% glycerol) by more than threefold compared to unreinforced controls. Transmission electron microscopy, spectroscopic techniques, and thermal analysis reveal that polyDOPA coatings influenced nanocomposite structure across multiple length scales, tripling the effective diameter of the CNC inclusions, reducing the tendency of CNC nanocrystals to aggregate, and increasing the glass transition temperature. The increase in glass transition temperature suggests reduced SPI molecular mobility, which, along with micromechanical modeling, indicates the potential for improved interfacial interactions. Results reveal how polyDOPA‐modified CNCs influence the interphase behavior and filler dispersion of SPI‐glycerol nanocomposites, providing a pathway to further improve their performance for various applications, including packaging, membranes, and coatings.

Summary Globally, weedy plants result in more crop yield loss than plant pathogens and insect pests combined. Much of the success of weeds rests with their ability to rapidly adapt in the face of human-mediated environmental management and change. The evolution of resistance to herbicides is an emblematic example of this rapid adaptation. Here, we focus on Alopecurus myosuroides (blackgrass), the most impactful agricultural weed in Europe. To gain insights into the evolutionary history and genomic mechanisms underlying adaptation in blackgrass, we assembled and annotated its large, complex genome. We show that non-target site herbicide resistance is oligogenic and likely evolves from standing genetic variation. We present evidence for divergent selection of resistance at the level of the genome in wild, evolved populations, though at the transcriptional level, resistance mechanisms are underpinned by similar patterns of up-regulation of stress- and defence-responsive gene families. These gene families are expanded in the blackgrass genome, suggesting that the large, duplicated, and dynamic genome plays a role in enabling rapid adaptation in blackgrass. These observations have wide significance for understanding rapid plant adaptation in novel stressful environments.