Biology subjects

Witte, K.

Publications and source records attributed to Witte, K..

4 recordsLinked to original sources

bioRxiv2025

Fingerprints as Frozen Nematic Fields

1Human fingerprints arise during embryogenesis and persist throughout life. While biochemical mechanisms of ridge initiation and growth are increasingly well understood, the physical principles governing ridge-pattern organisation remain unclear. Here, we show that fingerprint ridges can be treated as a frozen nematic field on a bounded surface, exhibiting long-range orientational order and singularities. Modelling ridge orientation as a two-dimensional nematic director field on the functional contact area of the fingertip, we apply a generalised Poincare-Hopf theorem to derive a topological constraint on permitted configurations. Triradii, loops, and whorls correspond to [Formula], [Formula], and +1 nematic defects, whose total charge is set by surface topology and boundary winding. Across 133 fingerprints from open-access databases, 95.5% satisfy the predicted charge-neutrality condition. Although boundary winding is typically below the idealised value (W{partial}S = 0.71 {+/-} 0.12 vs. W{partial}S {approx}1), fingerprints above a threshold (W{partial}S [≥] 0.6) consistently maintain zero net charge, revealing a coarse-grained realisation of the underlying topological rule. These results identify a mathematical limit on allowable fingerprint configurations and position fingerprints as a passive biological record of nematic order, with topology acting as a fundamental constraint on developmental pattern formation.

biophysics↗

bioRxiv2025

Differential receptor activation defines the fundamental limit of chemotactic sensing

1Cells are often assumed to require a [~]1% difference in ligand concentration across their length to bias chemotaxis, but this {Delta}C framework overlooks the non-linear relation between ligand concen-tration and receptor activation and, for linear gradients, is uninformative with respect to gradient steepness. Using mathematical modelling and experiments in linear gradients of the non-degradable cAMP analogue Sp-cAMPS, we show that ligand concentration alone does not describe chemotactic behaviour. By expressing signals as the differential proportion of activated receptors ({Delta}{Omega}), we find that cells can detect differences as small as 0.026% across their length. Importantly, the minimum differential required to induce bias increases with overall receptor activation, demonstrating that chemotactic sensitivity depends on the receptor occupancy regime rather than on {Delta}C. The true minimal chemotactic threshold therefore lies at concentrations that minimise receptor activation while still eliciting a bias, and is likely to be below 0.026%.

biophysics↗

bioRxiv2021

Paracrine role for endothelial IGF-1 receptor in white adipocyte beiging

There are at least two distinct types of thermogenic adipocyte in mammals: a pre-existing form established during development, termed classical brown adipocytes and an inducible form, beige adipocytes1-3. Various environmental cues can stimulate a process frequently referred to as beiging of white adipose tissue (WAT), leading to enhanced thermogenesis and obesity resistance 4, 5. Whilst beiging of WAT as a therapeutic goal for obesity and obesity-related complications has attracted much attention6-9; therapeutics stimulating beiging without deleterious side-effects remain elusive10. The endothelium lines all blood vessels and is therefore in close proximity to all cells. Many studies support the possibility that the endothelium acts as a paracrine organ11-14. We explored the potential role of endothelial insulin-like growth factor-1 receptor (IGF-1R) as a paracrine modulator of WAT phenotype. Here we show that a reduction in endothelial IGF-1R expression in the presence of nutrient excess leads to white adipocyte beiging, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell autonomous paracrine mechanism. We demonstrate that this is mediated by endothelial release of malonic acid, which we show, using prodrug analogues, has potentially therapeutically-relevant properties in the treatment of metabolic disease.

cell biology↗

bioRxiv2017

Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42*GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment.

cell biology↗