Publications

Neuromechanobiology has emerged as a multidisciplinary field at the interface of neuroscience and mechanobiology, aiming to elucidate how mechanical forces influence the development, organization, and function of the nervous system. This review offers a comprehensive overview of the historical evolution of the discipline, its molecular and biophysical foundations, and the experimental strategies employed to investigate it. Recent advances have revealed the pivotal roles of substrate stiffness, mechanical signaling, and force transduction in neural stem proliferation, axon guidance, synapse formation, and neural circuit maturation. All these effects originate at the molecular level and extend to the mesoscopic scale. Disrupted mechanotransduction has been increasingly implicated in neurodevelopmental disorders and neurodegenerative diseases, underscoring its clinical relevance. Key unresolved questions and future directions are also highlighted, with emphasis on the need for integrative approaches to decipher the complex interplay between mechanical forces and neural function.

JTD Keywords: Axon guidance, Brain development, Central-nervous-system, Contact inhibition, Force transmission, Hippo pathway, Human brain-development, Mechanical forces, Mechanical-properties, Mechanotransduction, Neural migration and regional specification, Neuromechanobiology, Patterned neural-tube, Pluripotent stem-cells, Signaling pathway, Synaptic activity, Tau mislocalization

Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.

JTD Keywords: axon growth, axon guidance, cell-migration, colorectal-cancer, dcc, dopaminergic-neurons, force-field, functional recovery, netrin-1, neurite outgrowth, neuronal maturation, neurotrophic factor, neurotrophicfactor mimetic, synapsis, Axon growth, Axons, Cells, cultured, Central nervous system, Coarse-grained model, Nanofibers, Netrin-1, Neurogenesis, Neuronal maturation, Neurons, Neurotrophic factor mimetic, Peptide amphiphile, Synapsis