Thrombo-inflammation analyzed in a validated seven-layer platelet decision model: cellular decisions are tough problems fast and heuristically solved

Author:

Prada Juan,Balkenhol JohannesORCID,Osmanoglu Özge,Afshar Maral,Kaltdorf Martin,Hofmann Sarah,von Mammen SebastianORCID,Heinze Katrin G.ORCID,Schulze HaraldORCID,Dandekar ThomasORCID

Abstract

AbstractDecisions in biology happen fast and are driven by evolution to optimize survival chances. In platelets, this is achieved by organizing signaling cascades into rapid decision-funnels with modulatory crosstalk. We show that network decision processes underlying cellular decisions are tough to solve (equivalent to classical satisfiability problems, SAT). Hence, heuristics, modular decision-making, and decision funnels are required for efficient decisions.We establish this using a seven-layer platelet decision network that agrees well with all available genetic and functional experimental data. Platelet decision cascades are robust to perturbations: For example, receptors such as TRPM7 modulate platelet activity. However, knockouts of the receptors still leave platelets reactive overall. Dynamic control resolves relaying functions from kinases to cytoskeleton alterations. This allows fast execution of platelet shape change or aggregation. Stress conditions can shift platelet decision funnels towards constant activation of aggregation or immune signaling, causing thrombosis or thrombo-inflammation. Based on the network dynamics, we conclude that platelets pragmatically resolve the complex (non-polynomial (NP)) cellular decision problems by using a similar relaxation to those proposed in mathematics – many different configurations end up in similar states. Metamathematical considerations (no mathematical proof) suggest that NP problems are more complex then P problems.One sentence abstractWe show that cellular decision problems like the platelet signaling cascade may need unexpectedly long to solve but in general, they are efficiently solved using heuristics (“decision funnels”), implying fast decisions but the risk of chronic stress and inflammation.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3