H2020Индивидуална стипендия2019–2021

BiFCCM · Bi-directional Force Communication on Cell-Matrix

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

Период: 2019-10-01 → 2021-10-13
Финансиране от ЕС: 178 320 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействията между клетките и тяхната среда се изучават чрез синтетични материали и микроскопия, за да се разбере как физическите сили влияят върху поведението им. Това помага при създаването на по-добри биоматериали за регенеративната медицина и тъканното инженерство.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Bi-directional Force Communication on Cell-Matrix

In tissue, cells are living in a 3D environment. Like planets in space, cells are not floating around and freely moving. Their movement and general behavior are governed by a variety of physical interactions. At the cellular level, these interactions comprise of molecular forces mediated by the mechanical reciprocity between the cell and the surrounding environment. These phenomena play a key role in cell migration and development, tissue regeneration and homeostasis, and pathologic changes. Mechanical reciprocity between cells and their surroundings is mostly observed in natural extracellular matrix (ECM), like collagen and fibrin gels. Natural ECMs possess a fibrous structure and complex nonlinear mechanics, including the strain–stiffening behavior, time-dependent viscoelasticity, and mechanical plasticity. However, the lower tunability of their bio/mechanical properties hinders the systematic study of the role of nonlinear mechanics in cell-matrix physical interactions. Moreover, the high degradability of natural ECMs does not allow the discrimination between physical interactions and enzyme-related biochemically remodeling. A comprehensive understanding of the interactions at the cell-matrix interface would enable the rational design of the next generation of biomaterials, with the goal of matching tissue and ECM properties for the development of improved in vitro models, and wide applications in regenerative medicine and tissue engineering. In the project, we combed a fibrous synthetic material with unique mechanical properties and advanced fluorescence microscopy techniques to investigate how cellular forces are related to the mechanical properties of the matrix, and how these affect cellular behavior.

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

Цел на проекта

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bi-directional mechanical exchange is crucial for many cell functions, is remains poorly understood, mostly since the majority of ECMs, both natural and synthetic, are difficult to control or lack biological relevance. A new synthetic polyisocyanide (PIC) gel is the first material that is an excellent mimic of the ECM (porous network architecture and nonlinear mechanics, including stiffening) and can independently tailor mechanical and biological properties. The gel is developed at Radboud University Nijmegen, where I finished my PhD. In this action, I want to study how forces from the cell or the ECM change the mechanical properties of the matrix and, more importantly, how this change affects biological functions. To this end, I will combine the unique, highly tunable PIC gels as synthetic ECM and study the matrix and cell behavior using advanced microscopic imaging techniques and spatial proteomics. Through PIC functionalization, I can tailor the size and number of focal adhesions (FAs), i.e. the protein complexes that link cells to the ECM. The forces generated by cells will be quantified both on cellular and single FA level by traction force microscope (TFM) and molecular tension sensor-based FRET. In addition, proteomic analysis will be performed to evaluate the effect of gels with different mechanical properties in the proteome. These results will have a high impact for understanding how cells interact with matrix through forces. Beyond my knowledge in biomaterials, I will gain new expertise in super-resolution microscope and mechanobiology at KU Leuven. This project highly matches the mission of the Marie Skłodowska-Curie Individual Fellowships to achieve two-way knowledge transfer and to promote my future career prospects.

Оригинален текст от CORDIS (на английски).

Участници

KATHOLIEKE UNIVERSITEIT LEUVEN · LeuvenКоординаторБелгия