PhD Discussions Sessions: Xarxa Quiroga and Adrián López

Biochemical responses to cell membrane mechanical remodelling

In a range of physiological processes, from extravasation to endocytosis, cells are constantly submitted to morphological changes, which eventually entail plasma membrane reshaping and adaptation. This remodelling could be harnessed by cells to detect and respond to shape changes, enabling mechanosensing mechanisms. However, how this occurs is still largely unknown.
To increase our understanding on how such process can happen, we have engineered a cell-stretching system that allows us to induce controlled plasma membrane remodelling while monitoring the whole process with the help of a microscope.
By using this set up, we have found that cell de-stretch triggers the formation of transient membrane evaginations whose resorption is actively regulated by BAR protein recruitment and actin polymerisation. The described process may be the first part of a molecular cascade used by cells in response to stretch.

Development of Microphysiological Systems for the Evaluation of Regenerative Therapies

The modelling of human organs has long been a task for scientist in order to lower the costs of therapeutic development and understand the pathological onset of human disease. Animal models remain the gold standard for drug discovery, despite their widely recognized limitations such as their marked differences with humans in terms of genetics and etiology or their high cost.

During the last decade, the advancements in tissue engineering and microfabrication gave rise to innovative models known as organs-on-a-chip or microphysiological systems, which aim to build functional miniaturized tissues in vitro that closely mimic the actual in vivo microenvironment. In this work, we will present two microphysiological platforms that we are developing with the goal of understanding and evaluating biomaterial-based regenerative therapies. The first model is aimed at replicating the bone healing microenvironment to evaluate the angiogenic potential of calcium-releasing scaffolds. The second model will be focused on the generation of an ischemic injury on a physiologically relevant cardiac tissue to test if lactate-releasing scaffolds are able to stimulate cardiac tissue regeneration.

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