Role of AL, FE, CU in the Alterations of Mechanical Properties of Cortical Neurons Probed by Atomic Force Microscopy

Abstract

Neurons are highly specialized cells primarily responsible for transmitting information through chemical and electrical signaling in both the central and the peripheral nervous system. Over the last few years there has been significant progress in understanding the role played by the substrate stiffness in neuronal growth, of the cell-substrate adhesion of forces, of the relationship between the neuron soma elastic properties and its health. The structural and mechanical properties of living neurons and their interaction with the surrounding environment such as the growth substrate, extracellular matrix, glial cells or other neurons can be evaluated by atomic force microscopy (AFM). This technique is able to image and interact with cells in physiologically relevant conditions at high spatial resolution, control forces applied to cells, measure cellular elastic properties and monitor variation in elastic modulus across living cells. Recent studies have demonstrated that Aluminum (Al), Iron (Fe), Copper (Cu) ions are involved in some neurodegenerative disorders. In particular Al concentration is increased in degenerating neurons in Alzheimer's disease (AD), Copper is involved in neurodegenerative disorders like familial amyotrophic lateral sclerosis, Alzheimer's or prion diseases, and accumulation of iron within senile plaques and neurofibrillary tangles is found in brains affected with AD. In this study we realize micro and nano scale maps of elastic modulus, adhesion forces and hysteresis of cortical neurons in the absence and in the presence of Al, Fe, Cu, ions at different concentrations by using AFM. We demonstrate that metal absorption causes variation of mechanical properties of neurons, implying a possible modification of cytoskeletal components, together with changes in cell-substrate adhesion forces and elastic properties.