Underestimated role of macromolecular crowding in bioengineered in vitro models of health and diseases

Macromolecular crowding (MMC) is a ubiquitous phenomenon in biological systems that is largely overlooked in bioengineered <i>in vitro</i> cellular models. This comprehensive review examines the significant impact of both intracellular and extracellular MMC on cellular and molecular processes under physiological and pathological conditions. By synthesizing current knowledge and identifying critical gaps in our understanding of MMC, this review highlights the need to incorporate crowding into the development of <i>in vitro</i> models for studying health and diseases, as well as for drug discovery platforms. The pervasive nature of MMC in biological systems underscores its potential importance in various physiological and pathological processes, including protein aggregation disorders, cancer, and vascular diseases. Recognizing the ubiquitous influence of MMC could open new avenues for therapeutic interventions and deepen our understanding of fundamental biological processes.