Biology subjects

Adeniran, I.

Publications and source records attributed to Adeniran, I..

3 recordsLinked to original sources

bioRxiv2026

Nanoscale spatial confinement of proton flux by cardiolipin drives high-speed lateral proton transport in mitochondria

Cellular respiration depends on the rapid, lateral flow of protons along the inner mitochondrial membrane to drive ATP synthesis. The precise nanoscale thermodynamic forces confining protons to this local circuit remain highly debated. Previous attempts to model macroscopic interfacial proton diffusion have been hindered by parameter equifinality and geometric artifacts, preventing the deconvolution of structural water networks from lipid electrostatics. Here, we resolve this ambiguity using a constrained, high-resolution two-dimensional continuum model. By incorporating experimentally validated buffer proton consumption rates as strict biological priors, we break mathematical degeneracy and isolate the specific thermodynamic components of planar lipid bilayers. Calibrating our model against time-resolved DOPG fluorescence kinetics, we decouple a universal structural water barrier (5.7 kBT) from the specific -1e electrostatic trap (4.3 kBT). Extrapolating these first principles, we predict the confinement architecture of cardiolipin, the signature -2e dimeric lipid of mitochondria. Our simulations reveal a deep kBT thermodynamic well. Crucially, this massive barrier confines protons within 1 to 2 nanometres of the membrane surface, virtually abolishing vertical leakage into the bulk aqueous phase of the inter-membrane space. We demonstrate that this spatial confinement triggers dimensional squeezing, preserving a robust lateral concentration gradient that actively accelerates radial proton wave propagation. Biologically, these findings reveal that cardiolipin does not merely prevent proton dissipation, it functions as a highly efficient, quasi-two-dimensional nanoscale antenna that captures and rapidly channels protons directly to ATP synthase, ensuring the kinetic viability of eukaryotic energy production.

biophysics↗

bioRxiv2026

Many-body quantum percolation sustains ohmic proton flux through the nanoconfined Fo motor

The FoF1-ATP synthase drives cellular bioenergetics by translocating protons across the inner mitochondrial membrane. We recently demonstrated that the lipid cardiolipin acts as a 2D antenna, actively funnelling protons into the nanoconfined Fo motor and enforcing severe "dimensional squeezing". This 1D nanoconfinement forces protons into such close proximity that their hydration shells physically overlap, theoretically generating an infinite classical steric gridlock. Yet, empirical measurements show the Fo motor operates at ~90% efficiency and exhibits barrierless, Ohmic conductance, presenting a biophysical paradox. To resolve this contradiction between classical physics and biological reality, we employed a differentiable inverse-physics framework to blindly deduce the proton wires geometry based solely on macroscopic physiological constraints: ohmic linearity and a 1.7 Deuterium Kinetic Isotope Effect. By substituting classical diffusion frameworks with a Many-Body Overdamped Quantum Langevin Equation (QLE), the optimiser successfully converged. It deduced that physiological flux dictates a steric boundary of 0.137 nm (aligning with the effective crystal radius of oxygen) and a structural confinement scale of 0.974 nm. We demonstrate that when these discovered biological parameters are evaluated under classical, independent-particle assumptions, the 1/r12 steric repulsive forces diverge to infinity, causing a simulation collapse. In contrast, the quantum mechanical nature of the QLE allows protons to exist as spatially spread-out clouds rather than fixed point particles. This enables them to traverse tight steric boundaries via a coordinated chain reaction similar to a frictionless nanoscale Newtons cradle. These findings prove that classical, independent-particle models are incompatible with the spatial confinement of respiratory complexes. We conclude that physiological proton transport through the Fo motor mandates a continuous quantum percolation channel, redefining our theoretical understanding of biological energy transduction. Statement of significanceThe FoF1-ATP synthase sustains cellular life by translocating protons across membranes, driven by its membrane-bound Fo motor. Within this motor, protons navigate a 1-2 nm water wire. Under this extreme biological nanoconfinement, classical physics predicts a structural "traffic jam", i.e., protons should gridlock due to the repulsive overlap of their hydration shells. Yet, the motor operates with highly efficient, ohmic conductance. Using a differentiable inverse-physics framework and the Many-Body Quantum Langevin Equation, we prove classical physics cannot resolve this steric gridlock. Instead, we demonstrate that physiological proton transport inherently mandates many-body quantum percolation. Protons navigate extreme nanoconfinement via spatial quantum delocalisation, establishing that biological energy transduction operates as a nanoscale quantum percolation channel.

biophysics↗

bioRxiv2023

An in silico cardiomyocyte reveals the impact of changes in CAMKII signalling on cardiomyocyte kinetics in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this in silico study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism and crossbridge cycling in HCM at the single cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways; and b) increased Ca2+ sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine to ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half sarcomere model, we also compared the fraction of detached, weakly bound and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply : demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.

systems biology↗