LamelliActin · Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2017-03-01 → 2019-02-28
- Финансиране от ЕС
- 178 157 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Мрежите от актин в предната част на движещите се клетки се изследват за това как реагират на физически прегради в тъканите. Разбирането на тези механизми помага при изучаването на рака, сърдечно-съдовите заболявания и хроничните възпаления.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
Many cells need to directionally migrate in response to external stimuli in order to accomplish their versatile functional tasks ranging from embryogenesis to wound healing and immune responses. On the other hand, misguidance of cell migration contributes to the pathogenesis of Europe’s socioeconomic most relevant diseases including cancer, cardiovascular diseases and chronic inflammation and better understanding the fundamental mechanisms of cell migration is of direct clinical relevance. While directional motion is typically dictated by chemotactic and haptotactic gradients, the actual motility within the organism is restricted by physical constraints, such as the presence of other cells and the extracellular matrix. Correspondingly, the ability to successfully navigate within confined environments in the presence of obstacles is an essential requirement for efficient cell migration within organisms. Lamellipodia are sheet-like protrusions of dendritic actin networks at the leading edge of migrating cells and inevitably the first cellular structures that encounter obstacles within their path of migration. Despite the well-established role of actin-rich lamellipodia in cell migration, the fundamental question of how lamellipodial actin-networks integrate local mechanical cues, like encountered obstacles into directional decision-making remains poorly understood. In particular, it remains to be determined how network-intrinsic processing of mechanical cues affects cell navigation with complex microenvironments like tissue. LammeliActin investigated this gap of knowledge by taking advantage of a combination of new experimental approaches. The data generated provides evidence for a yet unknown force generating actin-structure required for cell migration in confined microenvironments and paves the way for the development of novel pharmacological strategies to manipulate cell migration in vivo (Gaertner et al. in preparation).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Cell migration is centrally involved in embryonic development, regeneration and immune surveillance. However, when misguided it also contributes to the pathogenesis of Europe’s socioeconomic most relevant diseases including cancer, cardiovascular diseases and chronic inflammation. Accordingly, better understanding the fundamental mechanisms of cell migration is of direct clinical relevance. In order to migrate within a multicellular context, cells have to negotiate physical constraints, such as other cells and the extracellular matrix and effectively integrate mechanical challenges into directional decision-making. This proposal suggests a combined cell biological and biophysical approach to provide a quantitative understanding of the underlying molecular and mechanical principles. We will focus on the prototypic force-generating structure of migrating cells the lamellipodium - a flat sheet-like protrusion of dendritic actin networks at the leading front of migrating cells. We will decipher the ultrastructural adaptations of lamellipodial actin networks with single filament resolution and characterize how nucleation, elongation, depolymerization and crosslinking of actin filaments coordinate circumnavigation of mechanical obstacles. Technically, these questions will be addressed in a multidisciplinary approach by employing correlative fluorescence and electron tomography in combination with artificial environments engineered using microfluidics and substrate micropatterning, as well as genetic approaches and biological modelling. Importantly, findings will ultimately be challenged in living tissues. The expected results will generate an integrated view of force-adaptations of actin networks in living cells and will not only impact the fields of cell biology and biophysics but also cancer biology, immunology and developmental biology.
Оригинален текст от CORDIS (на английски).
Участници
- INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA · KlosterneuburgКоординаторАвстрия
Връзки
Данни: CORDIS, © Европейски съюз