Search for: All records

Mechanical forces provide critical biological signals to cells during healthy and aberrant organ development as well as during disease processes in adults. Within the cardiopulmonary system, mechanical forces, such as shear, compressive, and tensile forces, act across various length scales, and dysregulated forces are often a leading cause of disease initiation and progression such as in bronchopulmonary dysplasia and cardiomyopathies. Engineered in vitro models have supported studies of mechanical forces in a number of tissue and disease-specific contexts, thus enabling new mechanistic insights into cardiopulmonary development and disease. This review first provides fundamental examples where mechanical forces operate at multiple length scales to ensure precise lung and heart function. Next, we survey recent engineering platforms and tools that have provided new means to probe and modulate mechanical forces across in vitro and in vivo settings. Finally, the potential for interdisciplinary collaborations to inform novel therapeutic approaches for a number of cardiopulmonary diseases are discussed. 

In biological systems, chemical and physical transformations of engineered silver nanomaterials (AgENMs) are mediated, in part, by proteins and other biomolecules. Metalloprotein interactions with AgENMs are also central in understanding toxicity, antimicrobial, and resistance mechanisms. Despite their readily available thiolate and amine ligands, zinc finger (ZF) peptides have thus far escaped study in reaction with AgENMs and their Ag( i ) oxidative dissolution product. We report spectroscopic studies that characterize AgENM and Ag( i ) interactions with two ZF peptides that differ in sequence, but not in metal binding ligands: the ZF consensus peptide CP-CCHC and the C-terminal zinc finger domain of HIV-1 nucleocapsid protein p7 (NCp7_C). Both ZF peptides catalyze AgENM (10 and 40 nm, citrate coated) dissolution and agglomeration, two important AgENM transformations that impact bioreactivity. AgENMs and their oxidative dissolution product, Ag( i )(aq), mediate changes to ZF peptide structure and metalation as well. Spectroscopic titrations of Ag( i ) into apo-ZF peptides show an Ag( i )–thiolate charge transfer band, indicative of Ag( i )–ZF binding. Fluorescence studies of the Zn( ii )–NCp_7 complex indicate that the Ag( i ) also effectively competes with the Zn( ii ) to drive Zn( ii ) displacement from the ZFs. Upon interaction with AgENMs, Zn( ii ) bound ZF peptides show a secondary structural change in circular dichroism spectroscopy toward an apo-like structure. The results suggest that Ag( i ) and AgENMs may alter ZF protein function within the cell.