title: Fractal Characterization of Chromatin Decompaction in Live Cells.
abstract: Chromatin organization has a fundamental impact on the whole spectrum of genomic functions. Quantitative characterization of the chromatin structure, particularly at submicron length scales where chromatin fractal globules are formed, is critical to understanding this structure-function relationship. Such analysis is currently challenging due to the diffraction-limited resolution of conventional light microscopy. We herein present an optical approach termed inverse spectroscopic optical coherence tomography to characterize the mass density fractality of chromatin, and we apply the technique to observe chromatin decompaction in live cells. The technique makes it possible for the first time, to our knowledge, to sense intracellular morphology with length-scale sensitivity from ∼30 to 450 nm, thus primarily probing the higher-order chromatin structure, without resolving the actual structures. We used chromatin decompaction due to inhibition of histone deacytelases and measured the subsequent changes in the fractal dimension of the intracellular structure. The results were confirmed by transmission electron microscopy and confocal fluorescence microscopy.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois; Boston Medical Center, Department of Medicine, Boston University, Boston, Massachusetts.
authors.forename: Ji
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Stypula-Cyrus
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Blaha
authors.affiliation: Boston Medical Center, Department of Medicine, Boston University, Boston, Massachusetts.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois. Electronic address: v-backman@northwestern.edu.
authors.forename: Vadim
authors.initials: V
authors.lastname: Backman
mesh_terms: D002470:Cell Survival; D002843:Chromatin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D017709:Fractals; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D041622:Tomography, Optical; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid