An Active Biomechanical Model of Cell Adhesion Actuated by Intracellular Tensioning-Taxis.

Cell adhesion to the extracellular matrix (ECM) is highly active and plays a crucial role in various physiological functions. The active response of cells to physicochemical cues has been universally discovered in multiple microenvironments. However, the mechanisms to rule these active behaviors of cells are still poorly understood. Here, we establish an active model to probe the biomechanical mechanisms governing cell adhesion. The framework of cells is modeled as a tensional integrity that is maintained by cytoskeletons and extracellular matrices. Active movement of the cell model is self-driven by its intrinsic tendency to intracellular tensioning, defined as tensioning-taxis in this study. Tensioning-taxis is quantified as driving potential to actuate cell adhesion, and the traction forces are solved by our proposed numerical method of local free energy adaptation. The modeling results account for the active adhesion of cells with dynamic protruding of leading edge and power-law development of mechanical properties. Furthermore, the morphogenesis of cells evolves actively depending on actin filaments alignments by a predicted mechanism of scaling and directing traction forces. The proposed model provides a quantitative way to investigate the active mechanisms of cell adhesion and holds the potential to guide studies of more complex adhesion and motion of cells coupled with multiple external cues.

Dynamic effect of beta-amyloid 42 on cell mechanics.

Aß1-42, which is highly toxic to neural cells, is commonly present in the brains of people with Alzheimer's disease. In this study, dynamic changes in cell mechanics were monitored under Aß-induced toxicity. To investigate the changes in cellular mechanical properties, we used Aß1-42 oligomer at different concentrations to treat human neuroblastoma SH-SY5H cells. Results demonstrated a two-stage dynamic change in cell mechanics during neurodegeneration. Additionally, Young's modulus (YM) of the treated cells increased in a short period. The reasons include alteration in surface tension, osmotic pressure, and actin polymerization. Rough cellular membranes were observed from atomic force microscope (AFM) measurement. However, the cellular YM gradually decreased when the cells were continuously exposed to Aß1-42 or to a high concentration of Aß1-42. The major reason for the decreased YM was microtubule disassembly. Dynamic change in YM reflects different activities in cytoplasm in response to Aß1-42. The characteristic changes in cell mechanics provided insights into the dynamic neurodegeneration process of cells induced by Aß1-42 oligomer.

Multiplexed Optogenetic Stimulation of Neurons with Spectrum-Selective Upconversion Nanoparticles.

Optical modulation of nervous system becomes increasingly popular as the wide adoption of optogenetics. For these applications, upconversion materials hold great promise as novel photonic elements. This study describes an upconversion based strategy for combinatorial neural stimulation both in vitro and in vivo by using spectrum-selective upconversion nanoparticles (UCNPs). NaYF4 based UCNPs are used to absorb near-infrared (NIR) energy and to emit visible light for stimulating neurons expressing different channelrhodopsin (ChR) proteins. The emission spectrum of the UCNPs is selectively tuned by different doping strategy (Tm3+ or Er3+ ) to match the responsive wavelength of ChR2 or C1V1. When the UCNPs are packaged into a glass microoptrode, and placed close to or in direct contact with neurons expressing ChR2 or C1V1, the cells can be reliably activated by NIR illumination at single cell level as well as network level, which is characterized by patch-clamping and multielectrode-array recording in culture primary neurons. Furthermore, the UCNP-based optrode is implanted into the brain of live rodents to achieve all-optical remote activation of brain tissues in mammalian animals. It is believed that this proof-of-concept study opens up completely new applications of upconversion materials for regulating physiological functions, especially in neuroscience research.

Modeling the mechanics of cells in the cell-spreading process driven by traction forces.

Mechanical properties of cells and their mechanical interaction with the extracellular environments are main factors influencing cellular function, thus indicating the progression of cells in different disease states. By considering the mechanical interactions between cell adhesion molecules and the extracellular environment, we developed a cell mechanical model that can characterize the mechanical changes in cells during cell spreading. A cell model was established that consisted of various main subcellular components, including cortical cytoskeleton, nuclear envelope, actin filaments, intermediate filaments, and microtubules. We demonstrated the structural changes in subcellular components and the changes in spreading areas during cell spreading driven by traction forces. The simulation of nanoindentation tests was conducted by integrating the indenting force to the cell model. The force-indentation curve of the cells at different spreading states was simulated, and the results showed that cell stiffness increased with increasing traction forces, which were consistent with the experimental results. The proposed cell mechanical model provides a strategy to investigate the mechanical interactions of cells with the extracellular environments through the adhesion molecules and to reveal the cell mechanical properties at the subcellular level as cells shift from the suspended state to the adherent state.

Investigating dynamic structural and mechanical changes of neuroblastoma cells associated with glutamate-mediated neurodegeneration.

Glutamate-mediated neurodegeneration resulting from excessive activation of glutamate receptors is recognized as one of the major causes of various neurological disorders such as Alzheimer's and Huntington's diseases. However, the underlying mechanisms in the neurodegenerative process remain unidentified. Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale. Atomic force microscopy (AFM) is employed to measure the three-dimensional (3-D) topography and mechanical properties of live SH-SY5Y cells under stimulus of NMDA receptors. A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration. The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.