Dimethyl sulfoxide (DMSO) has been broadly used in biology as a cosolvent, a cryoprotectant, and an enhancer of membrane permeability, leading to the general assumption that DMSO-induced structural changes in cell membranes and their hydration water play important functional roles. Although the effects of DMSO on the membrane structure and the headgroup dehydration have been extensively studied, the mechanism by which DMSO invokes its effect on lipid membranes and the direct role of water in this process are unresolved. By directly probing the translational water diffusivity near unconfined lipid vesicle surfaces, the lipid headgroup mobility, and the repeat distances in multilamellar vesicles, we found that DMSO exclusively weakens the surface water network near the lipid membrane at a bulk DMSO mole fraction (XDMSO) of <0.1, regardless of the lipid composition and the lipid phase. Specifically, DMSO was found to effectively destabilize the hydration water structure at the lipid membrane surface at XDMSO <0.1, lower the energetic barrier to dehydrate this surface water, whose displacement otherwise requires a higher activation energy, consequently yielding compressed interbilayer distances in multilamellar vesicles at equilibrium with unaltered bilayer thicknesses. At XDMSO >0.1, DMSO enters the lipid interface and restricts the lipid headgroup motion. We postulate that DMSO acts as an efficient cryoprotectant even at low concentrations by exclusively disrupting the water network near the lipid membrane surface, weakening the cohesion between water and adhesion of water to the lipid headgroups, and so mitigating the stress induced by the volume change of water during freeze-thaw.

This work thereby presents a solution towards addressing a key challenge of implanting compliant neural probes using a two polymer system. PVA and PLGA are polymers with properties ideal for translation: commercially available, biocompatible with FDA-approved uses and bioresorbable. By presenting new ways to implant compliant neural probes, we can begin to fully evaluate their chronic biocompatibility and performance compared to traditional, rigid electronics.

Oppositely charged polyelectrolyte multilayers (PEMs) were built up in a layer-by-layer (LbL) assembly on top of the conducting polymer channel of an organic electrochemical transistor (OECT), aiming to combine the advantages of well-established PEMs with a high performance electronic transducer. The multilayered film is a model system to investigate the impact of biofunctionalization on the operation of OECTs comprising a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) film as the electrically active layer. Understanding the mechanism of ion injection into the channel that is in direct contact with charged polymer films provides useful insights for novel biosensing applications such as nucleic acid sensing. Moreover, LbL is demonstrated to be a versatile electrode modification tool enabling tailored surface features in terms of thickness, softness, roughness, and charge. LbL assemblies built up on top of conducting polymers will aid the design of new bioelectronic platforms for drug delivery, tissue engineering, and medical diagnostics.

In vitro electrophysiology using microelectrode arrays (MEAs) plays an important role in understanding fundamental biologic processes, screening potential drugs and assessing the toxicity of chemicals. Low electrode impedance and ability to sustain viable cultures are the key technology requirements. We show that MEAs consisting of poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) and coated with poly-L-lysine satisfy these requirements. Hippocampal cell cultures, maintained for 3-6 weeks on these MEAs, give high quality recordings of neural activity. This enables the observation of drug-induced activity changes, which paves the way for using these devices in in vitro drug screening and toxicology applications.

The influence of infrared laser pulses on intracellular Ca signaling was investigated in neural cell lines with fluorescent live cell imaging. The probe Fluo-4 was used to measure Ca in HT22 mouse hippocampal neurons and nonelectrically excitable U87 human glioblastoma cells exposed to 50 to 500 ms infrared pulses at 1470 nm. Fluorescence recordings of Fluo-4 demonstrated that infrared stimulation induced an instantaneous intracellular Ca transient with similar dose-response characteristics in hippocampal neurons and glioblastoma cells (half-maximal effective energy density EC of around 58 J.cm ). For both type of cells, the source of the infrared-induced Ca transients was found to originate from intracellular stores and to be mediated by phospholipase C and IP -induced Ca release from the endoplasmic reticulum. The activation of phosphoinositide signaling by IR light is a new mechanism of interaction relevant to infrared neural stimulation that will also be widely applicable to nonexcitable cell types. The prospect of infrared optostimulation of the PLC/IP cell signaling cascade has many potential applications including the development of optoceutical therapeutics.