The constant interplay and information exchange between cells and the microenvironment are essential to their survival and ability to execute biological functions. To date, a few leading technologies such as traction force microscopy, optical/magnetic tweezers, and molecular tension–based fluorescence microscopy are broadly used in measuring cellular forces. However, the considerable limitations, regarding the sensitivity and ambiguities in data interpretation, are hindering our thorough understanding of mechanobiology. Here, we propose an innovative approach, namely, quantum-enhanced diamond molecular tension microscopy (QDMTM), to precisely quantify the integrin-based cell adhesive forces. Specifically, we construct a force-sensing platform by conjugating the magnetic nanotags labeled, force-responsive polymer to the surface of a diamond membrane containing nitrogen-vacancy centers. Notably, the cellular forces will be converted into detectable magnetic variations in QDMTM. After careful validation, we achieved the quantitative cellular force mapping by correlating measurement with the established theoretical model. We anticipate our method can be routinely used in studies like cell-cell or cell-material interactions and mechanotransduction.
Keeping the stemness of human mesenchymal stem cells (hMSCs) and their adipocyte differentiation potential is critical for clinical use. However, these features are lost on traditional substrates. hMSCs have often been studied on stiff materials whereas culturing hMSCs in their native niche increases their potential. Herein, a patterned hydrogel nanocomposite with the stiffness of liver tissues is obtained without any molding process. To investigate hMSCs' mechanoresponse to the material, the RGD spacing units and the stiffness of the hydrogels are dually tuned via the linker length. This work suggests that hMSCs' locomotion is influenced by the nature of the hydrogel layer (bulk or thin film). Contrary to on bulk surfaces, cell traction occurs during cell spreading on thin films. In addition, hMSCs' spreading behavior varies from shorter to longer linker‐based hydrogels, where on both surfaces hMSCs maintains their stemness as well as their adipogenic differentiation potential with a higher number of adipocytes for nanocomposites with a longer polymer linker. Overall, this work addresses the need for a new alternative for hMSCs culture allowing the cells to differentiate exclusively into adipocytes. This material represents a cell‐responsive platform with a tissue‐mimicking architecture given by the mechanical and morphological properties of the hydrogel.
Bio-membranes exhibit complex but unique mechanical properties as communicative regulators in various physiological and pathological processes. Exposed to a dynamic micro-environment, bio-membranes can be seen as an intricate and delicate system. The systematical modeling and detection of their local physical properties are often difficult to achieve, both quantitatively and precisely. The recent emerging diamonds hosting quantum defects (i.e., nitrogen-vacancy (NV) center) demonstrate intriguing optical and spin properties, together with their outstanding photostability and biocompatibility, rendering them ideal candidates for biological applications. Notably, the extraordinary spin-based sensing enable the measurements of localized nanoscale physical quantities such as magnetic fields, electrical fields, temperature, and strain. These nanoscale signals can be optically read out precisely by simple optical microscopy systems. Given these exclusive properties, NV-center-based quantum sensors can be widely applied in exploring bio-membrane-related features and the communicative chemical reaction processes. This review mainly focuses on NV-based quantum sensing in bio-membrane fields. The attempts of applying NV-based quantum sensors in bio-membranes to investigate diverse physical and chemical events such as membrane elasticity, phase change, nanoscale bio-physical signals, and free radical formation are fully overviewed. We also discuss the challenges and future directions of this novel technology to be utilized in bio-membranes.
Geometric curvature critically regulates cellular behavior in soft tissue microenvironments, yet its role in mechanotransduction is underexplored due to stiffness-centric paradigms and challenges in creating stable curvatures on ultrasoft materials. We developed a solvent-induced buckling strategy to engineer multiaxial curvatures on ultrasoft hydrogels (500-750 Pa), recapitulating the anisotropic topologies of natural tissues such as cerebral gyri and breast lobules. Human mesenchymal stem cells on these surfaces exhibit robust focal adhesion maturation, cytoskeletal reorganization, nuclear mechanosensing (e.g., elevated Lamin A/C), and enhanced osteogenesis─phenotypes typically seen on rigid substrates but markedly attenuated on flat ultrasoft controls. This curvature-dominated mechanosensing persists in 3D injectable microgels, decoupling topological cues from the substrate stiffness. Mechanistic studies and energy minimization modeling reveal that curvature segregates stress fiber functions: basal fibers align circumferentially in high-curvature regions to enhance Rho-mediated contractility and focal adhesions, while apical fibers orient radially in low-curvature zones to minimize the bending energy. These findings establish topology as a primary driver of cellular tension and fate, providing fundamental insights into designing biomaterials and biointerfaces for soft tissue repair and regenerative medicine.
The conformal integration of nitrogen‐vacancy (NV) center nanodiamond arrays onto soft, hydrated, curvilinear biological interfaces remains a fundamental challenge for in vivo quantum sensing and imaging. Conventional transfer techniques often fail due to reliance on high temperature, corrosive chemicals, or mechanical peeling, leading to pattern damage, low fidelity, or poor biocompatibility. Here, we report a transfer strategy utilizing polyvinyl alcohol (PVA) soluble tape that enabling rapid, residue‐free, high‐fidelity transfer of nanodiamond patterns onto diverse biointerfaces. The success of this method is rooted in a unique “hydrate‐soften‐expand‐self‐peel” mechanism of the PVA backing. In situ mechanical tracking reveals non‐uniform PVA swelling generates transient normal and shear stresses at the interface. These stresses delaminate the tape within 3 min at room temperature while promoting adhesion of nanodiamonds to the substrate. In contrast, conventional tapes undergo passive dissolution and collapse, causing residue contamination and reduced efficiency. Leveraging this mechanism, we achieve conformal patterning on ultra‐soft hydrogels (∼0.6 kPa) and highly curved bio‐surfaces (hair, 100 µm −1 ). Additionally, we demonstrate a dual‐identity verification system integrating data storage and physical unclonable functions on a hydrogel contact lens. This work provides a versatile tool for bio‐interface engineering and a general framework for gentle, efficient transfer of functional nanomaterials.