HEИндивидуална стипендия2023–2024

TopCellComm · Topography-Mediated Cell Communication

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

Период: 2023-01-01 → 2024-12-31
Финансиране от ЕС: 214 934 €
Участници: 2
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Механичните взаимодействия между клетките и тяхната среда се изследват чрез процеси като разтягане или притискане, които влияят върху деленето и функцията им. Разбирането на тези сигнали може да подобри медицинските интервенции и стратегиите за възстановяване на увредени тъкани и органи.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Topography-Mediated Cell Communication

Mechanical interactions of cells with their environment are fundamental for cell- sensing and decision making in both development and homeostasis. Despite being widespread and acknowledged, the mechanisms by which cells perceive and generate forces remain elusive. In particular, the dynamic eedback that arises from interactions between cells and their substrate remains unexplored. In tissues, cells rely on the balance between internal pulling forces, dictated by tensions and cytoskeleton, and external forces that arise from the microenvironment. Mechanical forces impact protein distribution and gene expression within cells, inducing specific cell functions. For instance, stretching the cell results in enhanced cell division and differentiation in stem cells, whereas that mechanical compression governs the cell death and its subsequent expulsion from a tissue. Furthermore, cells not only respond to the environment, but actively modify it by exerting contractile forces generated by cross-bridging interactions of actin and myosin filaments while moving. Contractile forces cause rapid and long-ranged topographic anisotropies in the substrate, such as wrinkles or strains, which provide environmental cues and the means for substrate-mediated cell interactions. Such topography-mediated mechanical cell-cell communication has enormous potential both for improved medical interventions and for new strategies in regenerative medicine in which mechanical signals will be used o direct the repair of tissues and organs that have been damaged by trauma or disease. The overarching goal of this project is to model the phenomenon, in which cells autonomously exploit folding and topographical restructuring of their underlying substrates as a means of self-induced guidance and describe predicted topography-mediated cell-cell communication.

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

Цел на проекта

The processes through which cells sense, adapt, and respond to their environment are fundamental to development and homeostasis. Mechanical forces, exerted and experienced by cells, can act as messengers, however, the exact mechanisms by which cells perceive and generate forces have not been elucidated yet. Here, I aim to explore a phenomenon, in which cells autonomously exploit folding and topographical restructuring of their underlying substrates as a means of self-induced guidance and communication mechanism to coordinate their individual and collective behaviours. Guided by the Prof. Doostmohammadi groups recent collaborative study, revealing cell-generated forces from the folding patterns in real-time, I will develop a computational framework and will use it to numerically dissect the crosstalk between cell activity and self-generated patterns of substrate deformation. To model cell-generated forces, I will employ the phase-field formalism coupled will be coupled to the mathematical model of nonlinear substrate deformation. By utilising available data, I will calibrate the model and carry out simulations to uncover the underlying mechanics of single cell interactions with the substrate and emergent topographic anisotropies. I will then extend the model to consider interaction between pairs of cells on a substrate and elucidate the phenomena of topography-mediated cell communication. These actions will act as a first step towards the interconnection between multicellular-scale self-organized topographic modification and cell migration. Thus, this project at the intersection of mathematics, biology, and bioengineering will be a significant step towards delivering a state-of-the-art predictive tool for the design of biomaterials for regenerative medicine.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordОбединеното кралство