Tesi di laurea magistrale
Role of mechanical tension in neurite elongation
Corso di studi
BIOLOGIA APPLICATA ALLA BIOMEDICINA
relatore Prof.ssa Raffa, Vittoria
Data inizio appello
Data di rilascio
How axons elongate has been a central debate in neurobiology for decades. Recently, several studies have highlighted that mechanical tension can influence neuronal development, axonal sprouting and elongation. It has been proposed the hypothesis that mechanical tension could act as a second messenger, downstream most of chemical pathways involved in axonal growth, growth cone advancement and guidance. As opposite to the “tip growth model”, this hypothesis is consistent with a “stretch-growth model”, according to which, axonal growth at the leading edge of the growth cone is only a particular type of stretch-mediated axonal growth. This model is not still accepted as a unified method of axonal growth because there are still some contradictions and missing knowledge. For example, it was found that tension should exceed a threshold value to cause axonal initiation and elongation; forces below this threshold viscoelastically deform the neurites without growth. Previously works, showed that this threshold for PC12 cells is 10 nN. This threshold is too far from the resting tension of PC12 cell neurites and the range physiological tensions involved during neurite elongation (1-100 pN). In order to clarify this point, this work investigates the effect of low tensions (picoNewton forces) on neurite elongation of PC12 cells. To achieve this aim, we exploit a strategy recently developed in the team of Prof Raffa, consisting in the internalization of magnetic nanoparticles (MNP) by cells and generation of a tensile force under the effect of a static external magnetic field. The effect of such mechanical tension on neurite sprouting and elongation is investigated in different experimental conditions. We found that low tensions, thousandfold below the threshold identified by previous literature, can induce elongation, suggesting that there is no threshold for stretch-mediated axonal elongation. This support the understanding of the stretch-mediated growth model as a unified mechanism for axonal growth.
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