Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/519736

Optical determination of absolute membrane potential

Lazzari-Dean, J. R.·Gest, A. M. M.·Miller, E.
View original source ↗Export metadata ↓

Abstract

All cells maintain ionic gradients across their plasma membranes, producing transmembrane potentials (Vmem). Mounting evidence suggests a relationship between resting Vmem and the physiology of non-excitable cells with implications in diverse areas, including cancer, cellular differentiation, and body patterning. A lack of non-invasive methods to record absolute Vmem limits our understanding of this fundamental signal. To address this need, we developed a fluorescence lifetime-based approach (VF-FLIM) to visualize and optically quantify Vmem with single-cell resolution. Using VF-FLIM, we report Vmem distributions over thousands of cells, a 100-fold improvement relative to electrophysiological approaches. In human carcinoma cells, we visualize the voltage response to epidermal growth factor stimulation, stably recording a 10-15 mV hyperpolarization over minutes. Using pharmacological inhibitors, we identify the source of the hyperpolarization as the Ca2+-activated K+ channel Kca3.1. The ability to optically quantify absolute Vmem with cellular resolution will allow a re-examination of its roles as a cellular signal.

Explore related subjects

physiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lazzari-Dean, J. R., Gest, A. M. M., Miller, E.. 2019-01-14. Optical determination of absolute membrane potential. https://doi.org/10.1101/519736

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Androgen Receptor mediates beige adipocyte homeostasis and plasticity

Male adipose tissue undergoes profound post-pubertal remodeling characterized by the progressive transition of beige adipocytes toward a white adipocyte phenotype. Although androgen signaling has been implicated in adipose tissue biology, its role in beige adipocyte remodeling and metabolic plasticity remains poorly understood. Here we show that androgen receptor (AR) signaling is dynamically activated in inguinal white adipose tissue during the post-pubertal beige-to-white transition in male mice. Inducible deletion of AR in beige adipocytes impaired this remodeling process, resulting in the persistence of multilocular beige-like adipocytes despite reduced thermogenic competence and marked mitochondrial abnormalities. Transcriptomic and cistromic analyses identified AR as a direct regulator of adipocyte metabolic and differentiation programs, whereas immune-related transcriptional signatures in AR-deficient adipose tissue primarily reflected macrophage infiltration and inflammatory remodeling. Loss of AR promoted mitochondrial dysfunction, mitophagy, and altered glucose handling, while cell-autonomous AR silencing in beige adipocytes recapitulated key defects in mitochondrial organization and adipocyte identity. Longitudinal and metabolic challenge studies further demonstrated that AR signaling is required for age-associated adipose remodeling and adaptive beige adipocyte plasticity during high-fat diet feeding and cold exposure. Together, these findings identify AR as a central regulator of beige adipocyte remodeling, mitochondrial homeostasis, and adaptive metabolic function in male adipose tissue.

physiology↗
bioRxiv2026

Primary cilia coordinate c-KIT signaling induced proliferation in alpha cells

Circulating glucagon levels are elevated in patients with diabetes and obesity and contribute to hyperglycemia. The mechanisms underlying hyperglucagonemia remain poorly understood, but expansion of pancreatic -cell mass is thought to play an important role. Primary cilia are sensory organelles that act as signaling hubs, for pathways controlling cell differentiation, proliferation, and function, yet their contribution to -cell biology remains poorly defined. Here we investigated the role of primary cilia in the regulation of -cell proliferation. To this end we generated the first -cell primary cilia proteome identifying 167 cilia-enriched proteins. Among these, we identified and validated the proto-oncogene receptor tyrosine kinase, c-KIT, as a novel ciliary receptor in -cells. We further show that c-KIT signaling depends on intact primary cilia and that stimulation of isolated mouse islets with its endogenous ligand, stem cell factor (SCF), promotes -cell proliferation. In human pancreatic islets KITLG mRNA expression, but not KIT mRNA expression, correlated positively with donor BMI, suggesting that increased ligand availability drives c-KIT signaling in obesity. Together, our findings identify the primary cilium as a signaling platform c-KIT in cells and reveal a ciliary axis that may drive -cell expansion and hyperglucagonemia in obesity and diabetes.

physiology↗
bioRxiv2026

Passive thrust production in animal propulsion: exploitation of velocity gradients for energy conservation

Animals move through fluid environments that are rich in velocity gradients, yet how they exploit these flows to reduce locomotor costs remains elusive. We hypothesize that vertebrates utilize shear layers to passively produce thrust and establish a force equilibrium, thereby reducing locomotor cost. We discovered a shear-layer gait where fish preferentially position themselves within velocity gradients to maintain a steady posture and position at ~50% of their sustained maximum speed. Compared to the matching speed of uniform flow, fish moved into an adjacent velocity gradient reduced active propulsion effort by 98% and metabolic costs by 74%, reaching a resting state. The mechanism is a force equilibrium between viscous drag on the high-velocity side of the body and anteriorly directed suction forces on the low-velocity side, fundamentally a passive thrust production driven by the pressure gradients. Such discovery has direct applications in bioinspired propulsion design and broad implications for movement ecology.

physiology↗