Towards Biomimetic Biohybrid Synapses—Investigating the Role of Artificial Biomembranes Fluidity on Neuromorphic Short-Term Plasticity

Neurodegenerative diseases and brain damage require the constant development of new technologies able to replicate synaptic functionalities and replace damaged connections. As widely reported in literature, synaptic communication is based on electrochemical mechanisms: certain stimuli might induce the release of neurotransmitters from the pre-synaptic site and the consequent recognition of these molecules at the post-synaptic receptors, thus causing the propagation of an action potential from one cell to another.¹ In this scenario, neuromorphic devices represent a powerful platform to recreate artificial neural networks, which will offer the chance to improve implantable devices towards the replacement and repair of injured neuronal network areas. In particular, organic neuromorphic devices, such as PEDOT:PSS organic electrochemical transistor (OECT), offer a unique approach: in addition to the well-known biocompatibility of PEDOT:PSS, owing to its ionic-to-electronic current transduction, the conductance of these devices can be modulated through external stimuli (<i>i.e.</i> ionic flow) and the altered conductance state is retained over long time, replicating to some extent the physiological synaptic plasticity.² Recently we have successfully established a direct coupling between PC12 neuron-like cells, able to secrete dopamine (DA)³, and an organic neuromorphic device, thereby recreating an <i>in vitro</i> model of the synaptic system which simulate both long and short-term plasticity through the oxidation of DA.⁴ However, such biohybrid synapses still lack biomimetic features, which could promote their seamless integration within the neuronal network.<br/>Here, we aim to recapitulate not only the same functionalities of neurons (<i>i.e. </i>synaptic plasticity) using an organic neuromorphic device, but also to have a biomimetic platform replicating physiological cell membranes by means of supported lipid bilayers (SLBs). We investigated how the bilayer fluidity affects the ions flow towards the organic neuromorphic channel, thus modulating the de-doping level of PEDOT:PSS and the short-term memory of the neuromorphic OECT: For this reason, biomembranes with two different compositions were investigated: a fluid homogeneous bilayer formed by a single-type lipid molecule, and a more complex SLB which displays a higher rigidity and the same composition of biological neuronal membranes. We expect that according to lipids diffusion, such artificial bilayers could modulate differently the passage of ions through the membrane, with rigid SLB acting like a barrier and fluid membranes displaying a more sponge-like behavior. Furthermore, such platforms thanks to their learning capabilities and biomimetic properties, could really interact with biological cells, monitoring their activities and providing feedback accordingly, thus creating an artificial biohybrid functional network. This biohybrid platform might be further exploited to engineer future implantable devices able to replace damaged connections either in pathological networks in neurodegenerative diseases, or in case of amputations to create adaptive prosthetics able to reduce the mismatch between these artificial parts and the human body.<br/>References.<br/>1. Burns, M. E. & Augustine, G. J. Synaptic structure and function: Dynamic organization yields architectural precision. <i>Cell</i> <b>83</b>, 187–194 (1995).<br/>2. Gkoupidenis, P., Schaefer, N., Garlan, B. & Malliaras, G. G. Neuromorphic Functions in PEDOT:PSS Organic Electrochemical Transistors. <i>Adv. Mater.</i> <b>27</b>, 7176–7180 (2015).<br/>3. Westerink, R. H. S. & Ewing, A. G. The PC12 cell as model for neurosecretion. <i>Acta Physiol.</i> <b>192</b>, 273–285 (2008).<br/>4. Keene, S. T., Lubrano, C., Kazemzadeh, S., Melianas, A., Tuchman, Y., Polino, G., Scognamiglio, P., Cinà, L., Salleo, A., van de Burgt, Y., Santoro, F. A biohybrid synapse with neurotransmitter-mediated plasticity. <i>Nat. Mater.</i> (2020).