Fluctuations and Oscillatory Instabilities of Intracellular Fiber networks

by Jose Negrete JR
Doctoral thesis
Date of Examination:2014-12-03
Date of issue:2015-11-10
Advisor:Prof. Dr. Eberhard Bodenschatz
Referee:Prof. Dr. Eberhard Bodenschatz
Referee:Prof. Dr. Ulrich Parlitz
Persistent Address: http://dx.doi.org/10.53846/goediss-5361

 

 

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Abstract

English

Biological systems with their complex biochemical networks are known to be intrinsically noisy. The interplay between noise and dynamical behavior is particularly relevant in the case of chemotactic amoeboid cells as their cytoskeleton operates close to an oscillatory instability. Here, we investigate the oscillatory dynamics in the actin system of chemotactic amoeboid cells. We show that the large phenotypic variability in the polymerization dynamics can be accurately captured by a generic nonlinear oscillator model, in the presence of noise. The relative role of the noise is fully determined by a single dimensionless parameter, experimentally measurable, and whose distribution completely characterizes the possible cellular behavior. We find that cells operate either below or above the threshold of self-oscillation, always in a regime where noise plays a very substantial role. To test the limits of this phenomenological description, we perturbed experimentally the cytoskeletal dynamics by a short chemoattractant pulse and measured the spatio-temporal response of filamentous actin reporter,  LimE, and depolymerization regulators Coronin1 and Aip1. After pulsing, we observed self oscillating cells to relax back to their oscillatory state after a noisy transient. Particularly long transients were observed for cells initially displaying highly correlated oscillations. The observation of a slow recovery time of the actin polymerizing network provides a link to the long times scales, characteristic of chemotactic cell motility. In the second part of this work, we have characterized the response of LimE, Aip1, and Coronin to cAMP in non oscillating cells. We have used a proposed method that transforms the observed time series into symbolic dynamics, that gives partial information on the interactions between these proteins. We tested the predictions by studying the LimE response in mutant cells that either lacked Aip1 or Coronin. Finally, a model is proposed where Aip1 and Coronin synergizes to control actin polymerization.
Keywords: Biological Physics; Nonlinear Oscillations; Actin Cytoskeleton; Aip1; Coronin
 
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