H2020Индивидуална стипендия2020–2023

CellMechSensE · Cell mechanosensing in the extracellular matrix

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-06-01 → 2023-06-25
Финансиране от ЕС: 174 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Клетъчното усещане за механичните свойства на околната среда се изучава чрез анализ на взаимодействието между клетките и тъканите. Разбирането на този процес помага да се обясни как се развиват заболявания като диабет или метастази при рак.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Cell mechanosensing in the extracellular matrix

In our body, cells detect and respond to a variety of guiding cues from their extracellular environment. These signals ensure constant regulation of cellular behavior. However, if cells mis-interpret the signals and fail to perform their functional tasks, then disastrous effects, such as cancer metastasis or diabetes can take place. Recently, experiments using artificial cellular environments have established that key cell behaviors can strongly depend on the mechanics of their substrate. Thus, it is thought that cells perform mechanosensation: they probe their surroundings and adapt to the mechanical response they measure. Yet, a clear understanding of how cells perform mechanosensation in their natural extracellular matrix environment is still lacking. Indeed, the large inherent structural disorder of this network strongly limits the mechanical information that can be inferred from local cell-scale measurements. Moreover, the matrix also features an intricate nonlinear mechanical response that is largely unexplored at the cellular scale. This combination poses a puzzle for what information cells can glean by mechanically probing their ECM environment: How does the interplay between inherent nonlinearities and structural disorder physically limit cellular mechanosensation? This project aims at establishing a probing mechanism cells can employ to accurately infer the mechanical properties of their natural surroundings. We proposed a novel mechanism termed nonlinear mechanosensation, in which cells can actually take advantage of local nonlinearities to accurately sense their mechanical environment. This model relates local nonlinearities to macroscopic linear properties and brings new central theoretical knowledge to understand how cells behave individually and collectively by mechanically interacting with their surrounding environment.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Inside tissues, living cells can adhere to a heterogeneous fiber network, the extracellular matrix (ECM). Cells adjust their behavior in response to the local resistance they sense from pulling the neighboring fibers (mechanosensing). As they probe the network and respond to signals, cells can strongly distort the ECM and these deformations can serve as cues for other cells. The cell-generated forces can be large enough to trigger non-linear elastic effects and irreversible transformations of the ECM, resulting in drastic network remodeling. Yet, most theoretical studies have focused on small-force mechanical signals transmitted by an idealized static network. Therefore, the overall research aim of this proposal is to establish a theoretical framework to obtain fundamental understanding on how cells can exploit the non-linearities to extract accurate information by mechanically probing their surroundings. Recent advances in high-resolution, cell-scale imaging and measurement techniques now make it possible to calibrate quantitatively the model from experimental data and high computational power will permit a complete quantitative numerical study of the biological system. This project will bring understanding that will fill a crucial gap of knowledge on the mechanisms controlling individual and collective cell behavior, ultimately allowing key advances on our understanding of body functioning. This comprehension will have a major impact in guiding the design of biological implants and potentially avoid dramatic diseases. With this fellowship, I will extend my research area to biophysics and perform extensive computational simulations under the supervision of Prof. Broedersz. Conducting this research project will raise my academic profile as an expert in mechanical modeling of disordered networks. It will hence increase my chances to achieve my goal of becoming an independent research group leader in statistical modeling of disordered systems in France.

Оригинален текст от CORDIS (на английски).

Участници

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggКоординаторГермания