title: Enzyme-Instructed Self-Assembly for Spatiotemporal Profiling of the Activities of Alkaline Phosphatases on Live Cells.
abstract: Alkaline phosphatase (ALP), an ectoenzyme, plays important roles in biology. But there is no activity probes for imaging ALPs in live cell environment due to the diffusion and cytotoxicity of current probes. Here we report the profiling of the activities of ALPs on live cells by enzyme-instructed self-assembly (EISA) of a D-peptidic derivative that forms fluorescent, non-diffusive nanofibrils. Our study reveals the significantly higher activities of ALP on cancer cells than on stromal cells in their co-culture and shows an inherent and dynamic difference in ALP activities between drug sensitive and resistant cancer cells or between cancer cells with and without hormonal stimulation. Being complementary to genomic profiling of cells, EISA, as a reaction-diffusion controlled process, achieves high spatiotemporal resolution for profiling activities of ALPs of live cells at single cell level. The activity probes of ALP contribute to understanding the reversible phosphorylation/dephosphorylation in the extracellular domains that is an emerging frontier in biomedicine.
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Biology, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Berciu
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Hongjian
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Nicastro
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu