Cell-Cell Big Questions

Title: Mechanical intercellular communication via matrix-borne cell force transmission during vascular network formation

Problem or question being addressed:

The ability of cells to communicate and coordinate their activity is crucial to the development and homeostatic function of all tissues. Intercellular communication through receptor-ligand engagement at the cell-cell interface or via diffusive soluble factors has been extensively studied (1). In addition to these well established means of biochemically mediated intercellular signaling, a more recent body of evidence has shown that cells also communicate via cell-generated forces transmitted to neighboring cells through the extracellular matrix (ECM), which we term mechanical intercellular communication (MIC) (2, 3). The dynamic and reciprocal nature of generating and sensing mechanical signals, however, makes MIC difficult to investigate. Specifically, we lack an understanding of the cellular machinery required for cells to sense and respond to tensile forces originating from neighboring cells. Further, how tissue-relevant matrix properties mediate the…

Morphological and functional heterogeneity of endothelial cells: the chicken and the egg problem?

Problem or question being addressed

The anatomical heterogeneity of blood vessels in different organs has been long recognized [1] [2] [3]. ECs have been increasingly accepted as active players implicated in the regulation of many processes, rather than just a passive monolayer of conduit cells [4]. Vascular heterogeneity is essential in order to achieve such highly specialized functions, and can be displayed as a variety of features [5, 6]. Morphological heterogeneity is the most evident whereby ECs from arteries, veins, and capillaries differ in morphology, size, and orientation with respect to the direction of blood flow [7]. Additionally, the complexity in cellular morphology is different among organs and vascular beds. For example, ECs lining capillaries can be defined as continuous, fenestrated, and sinusoidal or discontinuous; and the distinct morphology of capillaries from different organs is closely related…

Title: Cell-cell communication and interaction with scRNA-seq and topology

1. Problem or questions being asked

Cell-cell communication is a challenging task since the interactions with the cells are quite complex and are difficult to understand or model with actual experiments or in silico methodologies.

Integrating different types of -omics is also a complex matter since different sources of data results in different treatments that could give completely different views of a system[1,2]. These sources need particular care when handled together so a system that automates the process could be the breakthrough in modeling complex systems and how tissue is formed and what are the interactions of its components, and cells.

Along the same path of complex systems and modeling, most of the methodologies in the field of cell-cell communication do not consider one of the most important sources of information about how the cells interact with each other, which is…