Optimality of Intercellular Signaling

Optimality of intercellular signaling: direct transport vs. diffusion. A mechanism is favored when it transports signaling molecules quickly as possible by small energy consumption.

Intercellular signaling has an important role in organism development, but not all communication occurs using the same mechanism. Here, we analyze the energy efficiency of intercellular signaling by two canonical mechanisms: diffusion of signaling molecules and direct transport mediated by signaling cellular protrusions. We find that the direct transport is favored over the diffusion when transporting a large amount of signaling molecules. There is a critical number of signaling molecules at which the efficiency of the two mechanisms are the same. The critical number is small when the distance between cells is far, which helps explain why protrusion-based mechanisms are observed in long-range cellular communications.

H Kim, Y Mori, and JB Plotkin, “Optimality of intercellular signaling: direct transport versus diffusion,” Submitted (2022) [arXiv]

Intrinsic Noise Initiates Cell Migration

Stochastic initiation of pressure-driven cell migration.

Blebs are cellular protrusions that appear as smooth spherical expansions of the membrane formed when it separates from the underlying actin cortex, driven by hydrostatic pressure generated in the cytoplasm by the contractile actomyosin cortex. In this project, we propose a model that the blebs are persistently developed by intrinsic noise, which comes from the assembly and turnover of the discrete cortical protein units. The dynamical system escapes the basin of attraction by accumulating the noise, as illustrated in the figure.

MJ Munoz-Lopez, H Kim, and Y Mori, “A Reduced 1D Stochastic Model of Bleb-driven Cell Migration,” (2022) Biophysical Journal. [DOI]

Cellular Extensions Optimally Find Targets

Persistent random walk for airineme search process. If the protrusion is persistent, then it could miss the target by wrong directions. On the contrary, if the protrusion is too diffusive, it twines too much to reach the target in given time.

Does the nature really favor optimality? Yes, it is when cells form the stripe patterns during zebrafish development. Sometimes on the yellow stripe, a black pigment cell is misallocated. In order to fix it, a different type of black pigment cells, called xantoblasts, extend long and thin protrusions called airinemes to reach the misallocated cell. One important parameter of this search process is the angular diffusion, which determines the “curviness” of airinemes. In this project, we have shown that the search process has the “optimal” angular diffusion in the sense of the search probability. Interestingly, the theoretical optimal value coincides with the experimental estimation.

S Park* and H Kim*, Y Wang, DS Eom, J Allard, “Zebrafish airineme shape is optimized between ballistic search and diffusive search,” (2022) eLife. [bioRxiv] [DOI]

Synaptic Patterns with Intrinsic Noise

Distribution of synaptic puncta along ventral cord of C. elegans. New synapses are inserted during development to maintain the synaptic density.

How intrinsic noise affects a pattern-forming mechanism? This has been studied extensively on the reaction-diffusion (RD) equation. Brooks and Bressloff (2016) developed C. elegans synaptic site pattern forming mechanism by introducing a reaction-diffusion-advection (RDA) equation. However, it has been still unknown what is the role of intrinsic fluctuation in the RDA stochastic pattern formation. In Kim and Bressloff (2020), we address this question by carrying out a system-size expansion of the RDA master equation.