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The response of cells to environmental stimuli, under either physiological or pathological conditions, plays a key role in determining cell fate toward either adaptive survival or controlled death. The efficiency of such a feedback mechanism is closely related to the most challenging human diseases, including cancer. Since cellular responses are implemented through physical forces exerted on intracellular components, more detailed knowledge of force distribution through modern imaging techniques is needed to ensure a mechanistic understanding of these forces. In this work, we mapped these intracellular forces at a whole-cell scale and with submicron resolution to correlate intracellular force distribution to the cytoskeletal structures. Furthermore, we visualized dynamic mechanical responses of the cells adapting to environmental modulations in situ. Such task was achieved by using an informatics-assisted atomic force microscope (AFM) indentation technique where a key step was Markov-chain Monte Carlo optimization to search for both the models used to fit indentation force–displacement curves and probe geometry descriptors. We demonstrated force dynamics within cytoskeleton, as well as nucleoskeleton in living cells which were subjected to mechanical state modulation: myosin motor inhibition, micro-compression stimulation and geometrical confinement manipulation. Our results highlight the alteration in the intracellular prestress to attenuate environmental stimuli; to involve in cellular survival against mechanical signal-initiated death during cancer growth and metastasis; and to initiate cell migration. Quantitative knowledge of internal force distribution in living cells is crucial to understand how cellular machinery responds mechanically to changes in the extracellular environment. Conventional force-sensing methods, which rely on pre-attached sensors, are incapable of providing whole-cell information with high spatial resolution. By machine learning assistance, we could improve AFM indentation's force sensitivity to a level that now enabled force (prestress) to be mapped on whole living cells with submicron resolution. The new capability revealed that cells actively redistribute forces among intracellular components to mitigate negative influence from the environment, and such response mechanisms could be used to understand ailing cellular states like cancer. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to examine the anti-biofilm activity and mechanism of gallic acid (GA), kaempferol-7-O-glucoside (K7G) and apigenin-7-O-glucoside (A7G) against Staphylococcus aureus and Escherichia coli. Methods: The antibacterial activity of the natural compounds was determined by serial dilution method. The inhibitory activity of natural compounds on biofilms was determined by crystal violet staining method. The effects and mechanisms of natural compounds on bacterial biofilms were analyzed by atomic force microscopy. Results: In our study, compared with GA and K7G, A7G was found to exhibit the strongest anti-biofilm and antibacterial activities. The minimum biofilm inhibitory concentration (MBIC) of A7G against S. aureus and E. coli was 0.20 mg/mL and 0.10 mg/mL, respectively. The inhibition rates of 1/2 MIC of A7G on biofilms of S. aureus and E. coli were 88.9%, and 83.2% respectively. Moreover, atomic force microscope (AFM) images showed the three-dimensional biofilm morphology of S. aureus and E. coli, and the results indicated that A7G was highly effective in biofilm inhibition. Discussion: It was found that the inhibition of A7G on biofilm was achieved through inhibiting on exopolysaccharides (EPS), quorum sensing (QS), and cell surface hydrophobicity (CSH). A7G exerted strong anti-biofilm activities by inhibiting EPS production, QS, and CSH. Hence, A7G, as a natural substance, could be a promising novel antibacterial and anti-biofilm agent for control of biofilm in food industry. [ABSTRACT FROM AUTHOR]

We conducted an in situ study on CFRP fracturing process using atomic-force-microscopy-based stress-sensitive indentation. Tensile stress distribution during fracture initiation and propagation was directly observed quantitatively. It led to a discovery that previously believed catastrophic fracture of individual carbon fiber develops in a controllable manner in the polymer matrix, exhibiting 10 times increase of fracture toughness. Plastic deformation in crack-bridging polymer matrix was accounted for the toughening mechanism. The model was applied to explain low temperature strength weakening of CFRP bulk material when matrix plasticity was intentionally 'shut down' by cryogenic cooling. [ABSTRACT FROM AUTHOR]

Elastic modulus measured through atomic force microscopy (AFM)-based indentation on single carbon fiber (CF) is found with dependence on lateral applied stress. An in situ indentation experiment inside a high-resolution transmission electron microscope was performed to quantitatively understand this phenomenon by observing microstructure change in the indented area. Change of graphitic basal plane misalignment angle during indentation was linked to a continuous change of modulus with the help of finite element simulation. The established relationship between modulus and indentation force was further used to calculate residual stress distribution in CF imbedded in a CF reinforced polymer composite using the AFM indentation technique. The stress-induced formation of nanoscale defects in the CF and their transformation into fracture were directly characterized. [ABSTRACT FROM AUTHOR]