Why does understanding the biology of fibroblasts in immunity really matter?

Fibroblasts are known for their ability to make and modify the extracellular matrix. However, there is more to them than meets the eye. It is now clear that they help define tissue microenvironments and support immune responses in organs. As technology advances, we have started to uncover the secrets of fibroblasts. In this Essay, we present fibroblasts as not only the builders and renovators of tissue environments but also the rheostat cells for immune circuits. Although they perform location-specific functions, they do not have badges of fixed identity. Instead, they display a spectrum of functional states and can swing between these states depending on the needs of the organ. As fibroblasts participate in a range of activities both in health and disease, finding the key factors that alter their development and functional states will be an important goal to restore homeostasis in maladapted tissues.

Isoprenoids enhance the stability of fatty acid membranes at the emergence of life potentially leading to an early lipid divide.

Two key problems concern cell membranes during the emergence and early evolution of life: what was their initial composition, and why did the membranes of archaea and bacteria diverge? The composition of the first cell membranes could shed light on the most likely environment for the emergence of life. The opposing stereochemistry of modern lipid glycerol-phosphate headgroups in bacteria and archaea suggests that early membranes were composed of single chain amphiphiles, perhaps both fatty acids and isoprenoids. We investigated the effect of adding isoprenoids to fatty acid membranes using a combination of UV-visible spectroscopy, confocal microscopy and transmission electron microscopy. We tested the stability of these membranes across a pH range and under different concentrations of ionic species relevant to oceanic hydrothermal environments, including Na2+, Cl-, Mg2+, Ca2+, HC O 3 - , Fe3+, Fe2+ and S2-. We also tested the assembly of vesicles in the presence of Fe particles and FeS precipitates. We found that isoprenoids enhance the stability of membranes in the presence of salts but require 30-fold higher concentrations for membrane formation. Intriguingly, isoprenoids strongly inhibit the tendency of vesicles to aggregate together in the presence of either Fe particles or FeS precipitates. These striking physical differences in the stability and aggregation of protocells may have shaped the divergence of bacteria and archaea in early hydrothermal environments.