Biology subjects

Pearce, D. J. G.

Publications and source records attributed to Pearce, D. J. G..

3 recordsLinked to original sources

bioRxiv2026

A novel reaction-diffusion architecture for engineering self-organized patterns in mammalian cells

Reaction-diffusion circuits generate self-organized spatial patterns through local activation and long-range inhibition, but synthetic implementations in mammalian cells have been limited by the differential-diffusion requirement. Here, we introduce a novel architecture, juxtacrine activation with paracrine inhibition (JAPI), where the activator propagates through cell-cell contacts rather than diffusion. We demonstrate mathematically and numerically that JAPI accesses the same patterning regimes as classical diffusion-based circuits with one fewer free parameter. We then engineer compact synNotch-based JAPI circuits in mammalian fibroblasts and demonstrate their sufficiency for self-organized patterning through tunable, size-limited signal propagation. Functionalized to spatially control morphogen secretion, these circuits perturb feather bud formation on adjacent embryonic chicken epidermis. Finally, we develop a library-based approach to explore coupled, dual-JAPI circuits with tunable cross-inhibition, enabling programmable interactions between patterns and access to a broad morphospace of spatial states. Together, JAPI provides a compact, modular platform for programming self-organized multicellular patterning. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/727552v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@fae8c9org.highwire.dtl.DTLVardef@c8eddborg.highwire.dtl.DTLVardef@177d08corg.highwire.dtl.DTLVardef@11cc952_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2019

ZapA stabilizes FtsZ filament bundles without slowing down treadmilling dynamics

For bacterial cell division, treadmilling filaments of FtsZ organize into a ring-like structure at the center of the cell. What governs the architecture and stability of this dynamic Z-ring is currently unknown, but FtsZ-associated proteins have been suggested to play an important role. Here, we used an in vitro reconstitution approach combined with fluorescence microscopy to study the influence of the well-conserved protein ZapA on the organization and dynamics of FtsZ filaments recruited to a supported membrane. We found that ZapA increases the spatial order and stabilizes the steady-state architecture of the FtsZ filament network in a highly cooperative manner. Despite its strong influence on their large-scale organization, ZapA binds only transiently to FtsZ filaments and has no effect on their treadmilling velocity. Together, our data explains how FtsZ-associated proteins can contribute to the precision and stability of the Z-ring without compromising treadmilling dynamics.

biophysics↗

bioRxiv2018

Cellular geometry controls the efficiency of motile sperm aggregates

Teams of cooperating sperm have been found across several vertebrate and invertebrate species, ranging from sperm pairs to massive aggregates containing hundreds of cells. Although the biochemical mechanisms involved in sperm-sperm adhesion are unclear, aggregation can enhance the motility of the cells. Here, we report a thorough computational investigation on the role of cellular geometry in the performance of sperm aggregates. The sperm head is modeled as a persistent random walker characterized by a non-trivial three-dimensional shape and equipped with an adhesive region where cell-cell binding occurs. By considering both a simple parametric head shape and a computer reconstruction of a real head shape based on morphometric data, we demonstrate that the geometry of the head and the structure of the adhesive region crucially affect both the stability and motility of the aggregates. Our analysis further suggests that the apical hook, commonly found in the sperm of most muroid rodents, might serve to shield portions of the adhesive region and promote efficient alignment of the velocities of the interacting cells.

evolutionary biology↗