Pockels Linear Electro-Optic Microscopy (PLEOM) for Cell Biology

Summary form only given. Membrane potential (MP) is a crucial biophysical parameter in the cell physiology, and new techniques to measure it are highly desired. It occurs at the cell membrane, which is a bilipid layer that acts as a barrier between extracellular fluid and the cytoplasm. There, the transport of specific ions and molecules, vital for the cell, is responsible for a difference of electrical potential between both sides of the layer, called MP. The MP can vary intrinsically in the case of neurons during an action potential, or for any cell under electrical perturbation. The phenomenon of electroporation for instance, which is mainly studied in the framework of cancer treatment, comes with the cancellation of MP after the creation of pores. The MP is later restored when the ions channels in the membrane start working again. In both cases, for cancerous cells and neurons, MP is traditionally measured using the patch clamp technique, invasive and lethal or using voltage-sensitive dyes, which are toxic at high concentration. In the general aim of measuring MPs without markers nor contact, we propose to adapt the Electro-Optical Microscopy technique (EOM). Indeed, EO contrast appears on the contour of the cell where the potential difference is providing by the membrane with the asymmetry necessary to sustain a Pockels effect. This effect manifests itself through a variation of the optical index of the material, proportional to the applied electric field. The EOM is an original microscopy scheme detecting and mapping, via interferometry, the Pockels' optical index variations. It allows doing the cartography of the electro-optic tensor (including its sign) on an inhomogeneous thin sample (like a cell culture). We intend to apply this principle to biological studies on cancerous treatment and neural activity.