Word games and molecular recognition - The creative control of endothelial cell function

In this paper we postulate that figures of language and structural features, which are characteristic of poetic writings and word games, have direct correlates in the cell/cell and cell/matrix recognition processes. We shall discuss the particular example of endothelial cells engagement into angiogenesis (the making of new blood vessels in adult vertebrates)-an activity that requires intense extracellular matrix (ECM) remodeling and Cell Adhesion Molecules (CAMs) rearrangement-to argue that angiogenesis controls are organized into semiotic dimensions. CAMs attach cells to the ECM; they are mainly composed of integrins (transmembrane receptors) that bind selectively to different ECM components. After ECM binding, the cytoplasmic tails of integrins within the cell will begin to interact with a wide range of recruited factors that, in turn, regulate integrin clustering in the cell membrane. These recruited factors also activate signaling pathways that link activated integrins to later microfilament system remodeling during cell migration. Ultimately CAMs work as functional protein networks-as the adaptor molecules in an organic code, the Adhesion Code-controlling cell migration/proliferation transition through the continual rearrangement of both ECM adhesion and Actin polymerization. Additionally, orchestrating the transition from clonal growth to differentiation, the interaction between CAMs and ECM components will trigger specific Signal Transduction pathways. We shall examine some attempts to conceptualize "somatic cell function" in the recent specialized literature, which introduces the notion of hierarchic organization into levels i.e. molecular, sub-cellular and cellular and describes an informational flow of increasing complexity versus decreasing number of entities through the levels. Beyond the syntactic level-the specific recognition of discrete ECM motifs by integrin heterodimers-we shall examine the semantic and pragmatic levels at which the composition and architecture of multimolecular complexes will dictate cell recognition events and cell fate decisions. These higher-level codes will be compared to the dynamics of the word games of Lewis Carroll, e.g. "doublets" and "magic squares." In such creative games words are subjected to synthetic transformations that have to conform to semantic rules, but are ultimately constrained by meaning, as concrete pragmatics. This gives us a model for analyzing angiogenesis control as a word game.