A Photoactivatable Formaldehyde Donor with Fluorescence Monitoring Reveals Threshold To Arrest Cell Migration

Abstract

Controlled light-mediated delivery of biological analytes can enable the investigation of highly reactivity molecules within living systems. As many biological effects are concentration dependent, it is critical to determine the location, time, and quantity of analyte donation. In this work, we have developed the first photoactivatable donor for formaldehyde (FA). Our optimized photoactivatable donor, photoFAD-3, is equipped with a fluorescence readout that enables monitoring of FA release with a concomitant 139-fold fluorescence enhancement. Tuning of photostability and cellular retention enabled quantification of intracellular FA release through cell lysate calibration. Application of photoFAD-3 uncovered the concentration range necessary for arresting wound healing in live cells. This marks the first report where a photoactivatable donor for any analyte has been used to quantify intracellular release.

Rational Design of Crystallization‐Induced‐Emission Probes To Detect Amorphous Protein Aggregation in Live Cells

“…However,i ntracellular amorphous protein aggregation with random and indefinite structure is usually envisioned to be "untargetable" or "undruggable" by small molecule probes,t hough they carry critical roles in cellular physiology and pathology.T he lack of defined structures for amorphous protein aggregates prevents them from being targeted by classic and novel design strategies for chemical sensors. [25][26][27][28][29][30][31][32][33] Another challenge for selective detection of amorphous aggregates is how to achieve selectivity over other organelles in the complex cellular milieu as they accumulate intracellularly rather than the extracellular space for amyloid aggregates.A lthough AIEgens exhibit appealing performance in detecting amyloid aggregated proteins,t hey failed to detect cellular amorphous ones without the covalent linkage to proteins exemplified by the seminal works from Hong and Zhang et al [34][35][36][37][38] Sensors of inherent selective binding towards amorphous aggregated proteins,h owever, were seldom reported. Thus,ab lueprint that guides us to design amorphous aggregated proteins sensors with controllable properties may be acomplementary puzzle piece for the field.…”

Rational Design of Crystallization‐Induced‐Emission Probes To Detect Amorphous Protein Aggregation in Live Cells

“…However, intracellular amorphous protein aggregation with random and indefinite structure is usually envisioned to be “untargetable” or “undruggable” by small molecule probes, though they carry critical roles in cellular physiology and pathology. The lack of defined structures for amorphous protein aggregates prevents them from being targeted by classic and novel design strategies for chemical sensors [25–33] . Another challenge for selective detection of amorphous aggregates is how to achieve selectivity over other organelles in the complex cellular milieu as they accumulate intracellularly rather than the extracellular space for amyloid aggregates.…”

New directions of activity-based sensing forin vivoNIR imaging

“…40 Recently, it has also been shown to inhibit wound healing when perturbing cellular concentrations at the micromolar level. 41 To study this reactive molecule, the probe design features a formaldehyde-responsive trigger that is based on 2-aza-Cope chemistry 42,43 and the NIR luminophore previously described ( Fig. 5a).…”