Cell-Intrinsic Adaptation of Lipid Composition to Local Crowding Drives Social Behaviour
Event details
| Date | 14.04.2015 |
| Hour | 08:30 |
| Speaker | Mathieu Fréchin, Ph.D., Pelkmans Lab, University of Zurich (CH) |
| Location | |
| Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
Cells sense the context in which they grow to adapt their phenotype and allow multicellular patterning by mechanisms of auto- and paracrine signalling. However, patterns also form in cell populations exposed to the same signalling molecules and substratum, which often correlate with specific features of the population context of single cells, such as local cell crowding. Here we reveal a cell-intrinsic molecular mechanism that allows multicellular patterning without requiring specific communication between cells. It acts by sensing the local crowding of a single cell through its ability to spread and activate FAK, resulting in adaptation of genes controlling membrane homeostasis. In cells experiencing low crowding, FAK suppresses transcription of the ABC transporter A1 by inhibiting FoxO3 and Tal1. Agent-based modelling and experimental confirmation identified membrane-based signalling and feedback control as crucial for the emergence of population patterns of ABCA1 expression, which adapts membrane lipid composition to cell crowding and affects multiple signalling activities, including the suppression of ABCA1 expression itself. The simple design of this cell-intrinsic system and its broad impact on the signalling state of single cells suggests a fundamental role for a tunable membrane lipid composition in collective cell behaviour.
Bio:
Mathieu was born in Thann, France. He did his PhD at the Institute of Molecular and Cellular Biology in Strasbourg, focusing on the structural, molecular and cellular aspects of mitochondrial translation both in yeast and human cells. Mathieu joined the Pelkmans Lab at University of Zurich in 2010 where he currently works on elucidating molecular mechanisms by which single cells adapt their phenotypic state to their social context.
Abstract:
Cells sense the context in which they grow to adapt their phenotype and allow multicellular patterning by mechanisms of auto- and paracrine signalling. However, patterns also form in cell populations exposed to the same signalling molecules and substratum, which often correlate with specific features of the population context of single cells, such as local cell crowding. Here we reveal a cell-intrinsic molecular mechanism that allows multicellular patterning without requiring specific communication between cells. It acts by sensing the local crowding of a single cell through its ability to spread and activate FAK, resulting in adaptation of genes controlling membrane homeostasis. In cells experiencing low crowding, FAK suppresses transcription of the ABC transporter A1 by inhibiting FoxO3 and Tal1. Agent-based modelling and experimental confirmation identified membrane-based signalling and feedback control as crucial for the emergence of population patterns of ABCA1 expression, which adapts membrane lipid composition to cell crowding and affects multiple signalling activities, including the suppression of ABCA1 expression itself. The simple design of this cell-intrinsic system and its broad impact on the signalling state of single cells suggests a fundamental role for a tunable membrane lipid composition in collective cell behaviour.
Bio:
Mathieu was born in Thann, France. He did his PhD at the Institute of Molecular and Cellular Biology in Strasbourg, focusing on the structural, molecular and cellular aspects of mitochondrial translation both in yeast and human cells. Mathieu joined the Pelkmans Lab at University of Zurich in 2010 where he currently works on elucidating molecular mechanisms by which single cells adapt their phenotypic state to their social context.
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