bims-ecemfi 2025-12-21 papers

Acta Biomater. 2025 Dec 15. pii: S1742-7061(25)00934-1. [Epub ahead of print]

A sulfonated cartilage interpenetrating polymer network reinforces and protects the extracellular matrix of degraded cartilage.

Christian D DeMoya, Pierson Husted, Dev R Mehrotra, Michael B Albro, Brian D Snyder, Mark W Grinstaff.

Cartilage extracellular matrix (ECM) comprises a type-II collagen fibril network that affords structure and tensile strength, complemented by a negatively charged, sulfated glycosaminoglycan (GAG) matrix that retains interstitial water. These components act synergistically, bestowing the rheological and tribological material properties essential to cartilage function. At the onset of osteoarthritis, a disease characterized by cartilage degeneration, GAGs diminish from the ECM reducing interstitial fluid load support (IFLS), equilibrium stiffness, and transferring load to the collagen fibril network, which subsequently breaks down, culminating in increased hydraulic permeability, and decreased cartilage stiffness. We restore the material properties of damaged cartilage critical to diarthrodial joint function by forming an interpenetrating polymer network (IPN) with the native collagen using a synthetic, hydrophilic, and biocompatible GAG-mimetic polymer. Upon visible light activation, the monomer, 3-sulfopropylmethacrylate (SPM), and the crosslinker, polyethylene glycol diacrylate (PEGDA), form a sulfonated and anionic IPN that fills the existing porous collagen matrix of degraded cartilage. Mechanistically, the highly sulfonated, anionic SPM IPN retards water transport, reestablishes collagen fibril network integrity, and restores tissue equilibrium stiffness, thereby returning the stiffness and viscoelastic properties of degraded cartilage to levels near healthy cartilage. Additionally, the SPM IPN protects cartilage reduces the infiltration of inflammatory cytokines that are known to upregulate catabolic matrix metalloproteinases and downregulate GAG production. STATEMENT OF SIGNIFICANCE: Amelioration of OA requires a comprehensive approach: neutralize or impede catabolic enzymes that degrade cartilage and reconstitute damaged cartilage by augmenting tissue ECM constituents. Currently, there are no clinical treatments that restore the viscoelastic material properties of hyaline cartilage tissue critical to its mechanical function and impart chondroprotection after OA induction. This work suggests that reconstituting GAG-depleted cartilage using a synthetic sulfonated interpenetrating polymer to reestablish IFLS instilled into the joint and polymerized with white light during conventional arthroscopy represents an effective, and minimally invasive strategy to restore the material properties of cartilage in the early stages of OA.

Keywords: cartilage; extracellular matrix; interpenetrating polymer network; osteoarthritis,

DOI: https://doi.org/10.1016/j.actbio.2025.12.028

ACS Synth Biol. 2025 Dec 17.

Force Transmission by Minimal Focal Adhesion Complexes Induces Synthetic Cell Deformation.

Natalie Huhn, Chiao-Peng Hsu, Timon Nast-Kolb, Arsenii Hordeichyk, Andreas R Bausch.

Cells sense and respond to mechanical cues through focal adhesions-dynamic, multiprotein assemblies linking the actin cytoskeleton to the extracellular matrix. These complexes are essential to processes from cell migration to tissue morphogenesis, yet the minimal physical requirements for their force-transmitting and mechanosensing functions remain unclear. Here, we reconstitute minimal focal adhesion-like complexes in giant unilamellar vesicles (GUVs) using kindlin-2, talin-1, FAK, paxillin, zyxin, and VASP anchored to membranes containing PIP2 and integrin β1 tails. These assemblies nucleate and anchor actin filaments into networks spanning the vesicle surface. Upon addition of nonmuscle myosin IIa, actomyosin contraction thickens filament bundles, aligns the complexes, and deforms the GUVs, while the assemblies remain stably membrane-bound. Our findings show that actin recruitment, force transmission, and structural stability under load can emerge from defined protein-membrane interactions alone. This minimal, three-dimensional platform offers a controllable synthetic biology system for probing mechanosensing and engineering force-responsive biomimetic systems.

Keywords: actin; actomyosin; contractile force transmission; focal adhesion; protein complex; reconstitution

DOI: https://doi.org/10.1021/acssynbio.5c00645

Immunol Rev. 2026 Jan;337(1): e70086

Mechanosensing in Dendritic Cells.

Vincent Calmettes, Melissa A Quintanilla, Livia Lacerda Mariano, Matthieu Piel, Hélène D Moreau, Ana-Maria Lennon-Duménil.

Since their discovery, dendritic cells have been recognized for their unusual capacity to sense and respond to physical stimuli within their environment. However, it took nearly two decades-and the advent of mechanobiology-to elucidate the underlying mechanisms and functional implications of this mechanical hypersensitivity. In this review, we first outline the fundamental principles by which cells interact with their physical surroundings and transduce mechanical cues into biological responses. We then examine these concepts in the context of dendritic cell biology, highlighting how mechanosensing shapes their immune phenotype and governs their migratory behavior across tissues. Emerging evidence reveals that dendritic cells possess remarkable adaptability to mechanical constraints, a property that critically defines their role in immune surveillance. These insights underscore the need to consider mechanical cues as key regulators of dendritic cell function, particularly in pathological settings where tissue mechanics are altered, such as cancer and fibrosis-associated autoimmune diseases.

Keywords: cell confinement; cell migration; cytoskeleton; dendritic cells; extracellular matrix; mechanosensing; nucleus; rigidity; tissue physical properties

DOI: https://doi.org/10.1111/imr.70086