scholarly journals Autoregulation of switching behavior by cellular compartment size

2021 ◽  
Author(s):  
Monika Jozsa ◽  
Tihol Ivanov Donchev ◽  
Rodolphe Sepulchre ◽  
Timothy O’Leary

Many kinds of cellular compartments comprise decision making mechanisms that control growth and shrinkage of the compartment in response to external signals. Key examples include synaptic plasticity mechanisms that regulate the size and strength of synapses in the nervous system. However, when synaptic compartments and postsynaptic densities are small such mechanisms operate in a regime where chemical reactions are discrete and stochastic due to low copy numbers of the species involved. In this regime, fluctuations are large relative to mean concentrations, and inherent discreteness leads to breakdown of mass action kinetics. Understanding how synapses and other small compartments achieve reliable switching in the low copy number limit thus remains a key open problem. We propose a novel self regulating signaling motif that exploits the breakdown of mass action kinetics to generate a reliable size-regulated switch. We demonstrate this in simple two and three-species chemical reaction systems and uncover a key role for inhibitory loops among species in generating switching behavior. This provides an elementary motif that could allow size dependent regulation in more complex reaction pathways and may explain discrepant experimental results on well-studied biochemical pathways.

2014 ◽  
Vol 11 (93) ◽  
pp. 20131100 ◽  
Author(s):  
Peter Banda ◽  
Christof Teuscher ◽  
Darko Stefanovic

State-of-the-art biochemical systems for medical applications and chemical computing are application-specific and cannot be reprogrammed or trained once fabricated. The implementation of adaptive biochemical systems that would offer flexibility through programmability and autonomous adaptation faces major challenges because of the large number of required chemical species as well as the timing-sensitive feedback loops required for learning. In this paper, we begin addressing these challenges with a novel chemical perceptron that can solve all 14 linearly separable logic functions. The system performs asymmetric chemical arithmetic, learns through reinforcement and supports both Michaelis–Menten as well as mass-action kinetics. To enable cascading of the chemical perceptrons, we introduce thresholds that amplify the outputs. The simplicity of our model makes an actual wet implementation, in particular by DNA-strand displacement, possible.


1989 ◽  
Vol 109 (6) ◽  
pp. 3493-3501 ◽  
Author(s):  
H Ertl ◽  
R Mengele ◽  
S Wenzl ◽  
J Engel ◽  
M Sumper

The extracellular matrix (ECM) of Volvox contains insoluble fibrous layers that surround individual cells at a distance to form contiguous cellular compartments. Using immunological techniques, we identified a sulfated surface glycoprotein (SSG 185) as the monomeric precursor of this substructure within the ECM. The primary structure of the SSG 185 poly-peptide chain has been derived from cDNA and genomic DNA. A central domain of the protein, 80 amino acid residues long, consists almost exclusively of hydroxyproline residues. The chemical structure of the highly sulfated polysaccharide covalently attached to SSG 185 has been determined by permethylation analysis. As revealed by EM, SSG 185 is a rod-shaped molecule with a 21-nm-long polysaccharide strand protruding from its central region. The chemical nature of the cross-links between SSG 185 monomers is discussed.


2015 ◽  
Vol 370 (1675) ◽  
pp. 20140289 ◽  
Author(s):  
Ulrich D. Kadolsky ◽  
Andrew J. Yates

What effect does the spatial distribution of infected cells have on the efficiency of their removal by immune cells, such as cytotoxic T lymphocytes (CTL)? If infected cells spread in clusters, CTL may initially be slow to locate them but subsequently kill more rapidly than in diffuse infections. We address this question using stochastic, spatially explicit models of CTL interacting with different patterns of infection. Rather than the effector : target ratio, we show that the relevant quantity is the ratio of a CTL's expected time to locate its next target (search time) to the average time it spends conjugated with a target that it is killing (handling time). For inefficient (slow) CTL, when the search time is always limiting, the critical density of CTL (that required to control 50% of infections, C * ) is independent of the spatial distribution and derives from simple mass-action kinetics. For more efficient CTL such that handling time becomes limiting, mass-action underestimates C * , and the more clustered an infection the greater is C * . If CTL migrate chemotactically towards targets the converse holds— C * falls, and clustered infections are controlled most efficiently. Real infections are likely to spread patchily; this combined with even weak chemotaxis means that sterilizing immunity may be achieved with substantially lower numbers of CTL than standard models predict.


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