Pingqiang Cai

Nanoparticles strengthen intracellular tension and retard cellular migration.

Nanoparticles can have profound effects on cell biology. Here, we show that after TiO2, SiO2, and hydroxyapatite nanoparticles treatment, TR146 epithelial cell sheet displayed slower migration. Cells after exposure to the nanoparticles showed increased cell contractility with significantly impaired wound healing capability however without any apparent cytotoxicity. We showed the mechanism is through nanoparticle-mediated massive disruption of the intracellular microtubule assembly, thereby triggering a positive feedback that promoted stronger substrate adhesions thus leading to limited cell motility.

Orthogonally engineering matrix topography and rigidity to regulate multicellular morphology

Programmable polymer substrates, which mimic the variable extracellular matrices in living systems, are used to regulate multicellular morphology, via orthogonally modulating the matrix topography and elasticity. The multicellular morphology is dependent on the competition between cell-matrix adhesion and cell-cell adhesion. Decreasing the cell-matrix adhesion provokes cytoskeleton reorganization, inhibits lamellipodial crawling, and thus enhances the leakiness of multicellular morphology.

Bio-Inspired Mechanotactic Hybrids for Orchestrating Traction-Mediated Epithelial Migration.

A platform of mechanotactic hybrids is established by projecting lateral gradients of apparent interfacial stiffness onto the planar surface of a compliant hydrogel layer using an underlying rigid substrate with microstructures inherited from 3D printed molds. Using this platform, the mechanistic coupling of epithelial migration with the stiffness of the extracellular matrix (ECM) is found to be independent of the interfacial compositional and topographical cues.

Gold nanotip array for ultrasensitive electrochemical sensing and spectroscopic monitoring.

A gold nanotip array platform with a combination of ultrasensitive electrochemical sensing and spectroscopic monitoring capability is reported. Adenosine triphosphate is detected down to 1 pM according to the impedance changes in response to aptamer-specific binding. Furthermore, the local molecular information can be monitored at the individual plasmonic nanotips, and hence provide the capability for a better understanding of complex biological processes.

Orientational Coupling Locally Orchestrates a Cell Migration Pattern for Re-Epithelialization

Re-epithelialization by collective migration of epithelial cells over a heterogeneous environment to restore tissue integrity and functions is critical for development and regeneration. Here, it is reported that the spatial organization of adjacent adherent paths within sparsely distributed extracellular matrix (ECM) has a significant impact on the orientational coupling between cell polarization and collective cell migration. This coupling effect determines the migration pattern for human keratinocytes to regain their cohesion, which impacts the occupancy of epithelial bridge and the migration velocity in wound repair. Statistical studies suggest the converging organization of ECM, in which adjacent paths become closer to each other and finally converge to a junctional point, facilitating collective cell migration mostly within variable ECM organization, as the polarization of the advancing cell sheet is remodeled to align along the direction of cell migration. The findings may help to design implantable ECM to optimize efficient skin regeneration.

Nanomechanically Visualizing Drug–Cell Interaction at the Early Stage of Chemotherapy

A detailed understanding of chemotherapy is determined by the response of cell to the formation of the drug-target complex and its corresponding sudden or eventual cell death. However, visualization of this early but important process, encompassing the fast dynamics as well as complex network of molecular pathways, remains challenging. Herein, we report that the nanomechanical traction force is sensitive enough to reflect the early cellular response upon the addition of chemotherapeutical molecules in a real-time and noninvasive manner, due to interactions between chemotherapeutic drug and its cytoskeleton targets. This strategy has outperformed the traditional cell viability, cell cycle, cell impendence as well as intracellular protein analyses, in terms of fast response. Furthermore, by using the nanomechanical traction force as a nanoscale biophysical marker, we discover a cellular nanomechanical change upon drug treatment in a fast and sensitive manner. Overall, this approach could help to reveal the hidden mechanistic steps in chemotherapy and provide useful insights in drug screening.

Role of Cytoskeletal Tension in the Induction of Cardiomyogenic Differentiation in Micropatterned Human Mesenchymal Stem Cell

The role of biophysical induction methods such as cell micropatterning in stem cell differentiation has been well documented previously. However, the underlying mechanistic linkage of the engineered cell shape to directed lineage commitment remains poorly understood. Here, it is reported that micropatterning plays an important role in regulating the optimal cytoskeletal tension development in human mesenchymal stem cell (hMSC) via cell mechanotransduction pathways to induce cardiomyogenic differentiation. Cells are grown on fibronectin strip patterns to control cell polarization and morphology. These patterned cells eventually show directed commitment toward the myocardial lineage. The cells mechanical properties (cell stiffness and cell traction forces) are observed to be very different for cells that have committed to the myocardial lineage when compared with that of control. These committed cells have mechanical properties that are significantly lower indicating a correlation between the micropatterning-induced differentiation and actomyosin-generated cytoskeletal tension within patterned cells. To study this correlation, patterned cells are treated with RhoA pathway inhibitor. Severely down-regulated cardiomyogenic marker expression is observed in those treated patterned cells, thus emphasizing the direct dependence of hMSCs differentiation fate on the cytoskeletal tension.

Nanomechanical Force Mapping of Restricted Cell-To-Cell Collisions Oscillating between Contraction and Relaxation

Contact-mediated cell migration strongly determines the invasiveness of the corresponding cells, collective migration, and morphogenesis. The quantitative study of cellular response upon contact relies on cell-to-cell collision, which rarely occurs in conventional cell culture. Herein, we developed a strategy to activate a robust cell-to-cell collision within smooth muscle cell pairs. Nanomechanical traction force mapping reveals that the collision process is promoted by the oscillatory modulations between contraction and relaxation and orientated by the filopodial bridge composed of nanosized contractile machinery. This strategy can enhance the occurrence of cell-to-cell collision, which renders it advantageous over traditional methods that utilize micropatterned coating to confine cell pairs. Furthermore, modulation of the balance between cell tugging force and traction force can determine the repolarization of cells and thus the direction of cell migration. Overall, our approach could help to reveal the mechanistic contribution in cell motility and provide insights in tissue engineering.

Mechano-Based Transductive Sensing for Wearable Healthcare

Wearable healthcare presents exciting opportunities for continuous, real-time, and noninvasive monitoring of health status. Even though electrochemical and optical sensing have already made great advances, there is still an urgent demand for alternative signal transformation in terms of miniaturization, wearability, conformability, and stretchability. Mechano-based transductive sensing, referred to the efficient transformation of biosignals into measureable mechanical signals, is claimed to exhibit the aforementioned desirable properties, and ultrasensitivity. In this Concept, a focus on pressure, strain, deflection, and swelling transductive principles based on micro-/nanostructures for wearable healthcare is presented. Special attention is paid to biophysical sensors based on pressure/strain, and biochemical sensors based on microfluidic pressure, microcantilever, and photonic crystals. There are still many challenges to be confronted in terms of sample collection, miniaturization, and wireless data readout. With continuing efforts toward solving those problems, it is anticipated that mechano-based transduction will provide an accessible route for multimode wearable healthcare systems integrated with physical, electrophysiological, and biochemical sensors.

Biomechano‐Interactive Materials and Interfaces

The reciprocal mechanical interaction of engineered materials with biointerfaces have long been observed and exploited in biomedical applications. It contributes to the rise of biomechano-responsive materials and biomechano-stimulatory materials, constituting the biomechano-interactive interfaces. Here, endogenous and exogenous biomechanical stimuli available for mechanoresponsive interfaces are briefed and their mechanistic responses, including deformation and volume change, mechanomanipulation of physical and chemical bonds, dissociation of assemblies, and coupling with thermoresponsiveness are summarized. The mechanostimulatory materials, however, are capable of delivering mechanical cues, including stiffness, viscoelasticity, geometrical constraints, and mechanical loads, to modulate physiological and pathological behaviors of living tissues through the adaptive cellular mechanotransduction. The biomechano-interactive materials and interfaces are widely implemented in such fields as mechanotriggered therapeutics and diagnosis, adaptive biophysical sensors, biointegrated soft actuators, and mechanorobust tissue engineering, which have offered unprecedented opportunities for precision and personalized medicine. Pending challenges are also addressed to shed a light on future advances with respect to translational implementations.