Although many details remain still elusive, it became increasingly evident in recent years that mechanosensing of microenvironmental biophysical cues and subsequent mechanotransduction are strongly involved in the regulation of neuronal cell development and functioning. This review gives an overview about the current understanding of brain and neuronal cell mechanobiology and how it impacts on neurogenesis, neuronal migration, differentiation, and maturation. We will focus particularly on the events in the cell/microenvironment interface and the decisive extracellular matrix (ECM) parameters (i.e. rigidity and nanometric spatial organisation of adhesion sites) that modulate integrin adhesion complex-based mechanosensing and mechanotransductive signalling. It will also be outlined how biomaterial approaches mimicking essential ECM features help to understand these processes and how they can be used to control and guide neuronal cell behaviour by providing appropriate biophysical cues. In addition, principal biophysical methods will be highlighted that have been crucial for the study of neuronal mechanobiology.
The study shows, by exploiting a novel adhesion force spectroscopy approach, that microenvironmental nanotopography impacts strongly on integrin-mediated cellular mechanosensing, by influencing adhesion site force loading dynamics.
Atomic force microscopy (AFM) is a powerful tool to investigate interaction forces at the micro and nanoscale. Cantilever stiffness, dimensions and geometry of the tip can be chosen according to the requirements of the specific application, in terms of spatial resolution and force sensitivity. Colloidal probes (CPs), obtained by attaching a spherical particle to a tipless (TL) cantilever, offer several advantages for accurate force measurements: tunable and well-characterisable radius; higher averaging capabilities (at the expense of spatial resolution) and sensitivity to weak interactions; a
The crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as, e.g., vinflunine (VFL), colchicine (COL), and...
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