ABSTRACT
Extensive studies have shown that cells can sense and modulate the biomechanical properties of the ECM within their resident microenvironment. Thus, targeting the mechanotransduction signaling pathways provides a promising way for disease intervention. However, how cells perceive these mechanical cues of the microenvironment and transduce them into biochemical signals remains to be answered. Förster or fluorescence resonance energy transfer (FRET) based biosensors are a powerful tool that can be used in live-cell mechanotransduction imaging and mechanopharmacological drug screening. In this review, we will first introduce FRET principle and FRET biosensors, and then, recent advances on the integration of FRET biosensors and mechanobiology in normal and pathophysiological conditions will be discussed. Furthermore, we will summarize the current applications and limitations of FRET biosensors in high-throughput drug screening and the future improvement of FRET biosensors. In summary, FRET biosensors have provided a powerful tool for mechanobiology studies to advance our understanding of how cells and matrices interact, and the mechanopharmacological screening for disease intervention.
ABSTRACT
Eyewitness misidentification accounts for 70% of verified erroneous convictions. To address this alarming phenomenon, research has focused on factors that influence likelihood of correct identification, such as the manner in which a lineup is conducted. Traditional lineups rely on overt eyewitness responses that confound two covert factors: strength of recognition memory and the criterion for deciding what memory strength is sufficient for identification. Here we describe a lineup that permits estimation of memory strength independent of decision criterion. Our procedure employs powerful techniques developed in studies of perception and memory: perceptual scaling and signal detection analysis. Using these tools, we scale memory strengths elicited by lineup faces, and quantify performance of a binary classifier tasked with distinguishing perpetrator from innocent suspect. This approach reveals structure of memory inaccessible using traditional lineups and renders accurate identifications uninfluenced by decision bias. The approach furthermore yields a quantitative index of individual eyewitness performance.