Abstract
Cell migration is driven by propulsive forces derived from polymerizing actin that pushes and extends the plasma membrane. The underlying actin network is constantly undergoing adaptation to new mechano-chemical environments and intracellular conditions. As such, mechanisms that regulate actin dynamics inherently contain multiple feedback loops and redundant pathways. Given the highly adaptable nature of such a system, studies that use only perturbation experiments (e.g. knockdowns, overexpression, pharmacological activation/inhibition, etc.) are challenged by the nonlinearity and redundancy of the pathway. In these pathway configurations, perturbation experiments at best describe the function(s) of a molecular component in an adapting (e.g. acutely drug-treated) or fully adapted (e.g. permanent gene silenced) cell system, where the targeted component now resides in a non-native equilibrium. Here, we propose how quantitative live-cell imaging and analysis of constitutive fluctuations of molecular activities can overcome these limitations. We highlight emerging actin filament barbed-end biology as a prime example of a complex, nonlinear molecular process that requires a fluctuation analytic approach, especially in an unperturbed cellular system, to decipher functional interactions of barbed-end regulators, actin polymerization and membrane protrusion. This article is part of the theme issue ‘Self-organization in cell biology’.
Original language | English (US) |
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Article number | 20170110 |
Journal | Philosophical Transactions of the Royal Society B: Biological Sciences |
Volume | 373 |
Issue number | 1747 |
DOIs | |
State | Published - May 26 2018 |
Keywords
- Actin
- Fluctuations
- Imaging
- Real-time
- Signalling
- System redundancy
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Agricultural and Biological Sciences