Fig. 3.

Dysregulation of plasma membrane domains and the role of MTDBs as countermeasures for loss of membrane homeostasis. Plasma membrane domain biochemical and biophysical homeostasis, e.g., membrane order, proteolipid clustering, and precise spatial compartmentalization of signaling components, regulates intracellular signaling. a In healthy cells, membrane domains display “normal” levels of order and proteolipid clustering and signaling-associated effectors localize at the right place in the right time. Together, this ensures canonical cell signaling. b During cancer, alterations of membrane domain features are observed such as increased membrane order, clustering, and effector recruitment as well as mislocalization of domain effectors. Loss of membrane domain homeostasis leads to an atypical cellular state, thus driving aberrant signaling. c Interestingly, MTDBs have the ability to target and reshape plasma membrane domains. In some cases, MTDBs have been shown to alter membrane fluidity, proteolipid complexes, and effector localization and suppress oncogenic signaling. In this way, MTDBs are able to restore, to a significant extent, healthy cell signaling