Scanning Probe Microscopy Unit

The Scanning Probe Microscopy Unit of the BEPS Shared Resource specializes in the following:

Sub-nm resolution imaging of molecular complexes, supported lipid bilayers, cells, and tissues
Molecular recognition, protein unfolding
Force spectroscopy, visco-elastic properties
Simultaneous, co-localized AFM and fluorescence (including TIRF and confocal) microscopy
Mathematical modeling, finite element analysis

We are located in Building 13 on the NIH campus.

Atomic Force Imaging and Spectroscopy

AFM:

Sub-nm resolution imaging of macromolecular complexes (including protein-protein, protein-DNA, and/or RNA), supported lipid bilayers, cells and tissues under ambient conditions
Force spectroscopy: nano-indentation strategies to map viscoelastic, adhesion and other properties at nm resolution (including single molecules, lipid bilayers, live cells and tissues)
Studies of protein unfolding

Molecular Recognition: Antigen recognition by binding events with antibody-functionalized probes. Immuno-AFM: Molecular recognition of protein-antibody complexes by direct AFM imaging. Co-localized immuno-fluorescence and immuno-AFM.

Mathematical Modeling: Mathematical modeling of biophysical systems, image analysis methodologies, finite element analysis.

Auditory Mechanics:

Project examples

Nucleus mechanical properties of HMGN5 over-expressing cells (Dr. M. Bustin, CCR, NCI)

Cell visco-elastic properties were measured on live cells with the AFM

Novel DNA-RNA complexes (Dr. S. Adhya, CCR, NCI)

Novel bacterial RNA binds and bridges DNA double-strands

Emilios K Dimitriadis

Defining essential charged residues in fibril formation of a lysosomal derived N-terminal α-synuclein truncation.

McGlinchey RPRamos SDimitriadis EKWilson CBLee JC

Nat Commun

2025 Apr 23

Perivascular cells function as key mediators of mechanical and structural changes in vascular capillaries.

Franca CMLima Verde MESilva-Sousa ACMansoorifar AAthirasala ASubbiah RTahayeri ASousa MFraga MAVisalakshan RMDoe ABeadle KFinley MDimitriadis EBays JUroz MYamada KMChen CBertassoni LE

Sci Adv

2025 Jan 10

HIV-1 Integrase Assembles Multiple Species of Stable Synaptic Complex Intasomes That Are Active for Concerted DNA Integration In vitro.

Li MYang RChen XWang HGhirlando RDimitriadis EKCraigie R

J Mol Biol

2024 May 15

A novel cysteine-rich adaptor protein is required for mucin packaging and secretory granule stability in vivo.

Zhang LMuirhead KJSyed ZADimitriadis EKTen Hagen KG

Proc Natl Acad Sci U S A

2024 Feb 06

Sulfated endospermic nanocellulose crystals prevent the transmission of SARS-CoV-2 and HIV-1.

Carvajal-Barriga EJFitzgerald WDimitriadis EKMargolis LFields RD

Sci Rep

2023 Apr 28

Sulfated endospermic nanocellulose crystals prevent the transmission of SARS-CoV-2 and HIV-1.

Barriga EJCFitzgerald WDimitriadis EKMargolis LFields RD

Res Sq

2022 Oct 28

A phage-encoded nucleoid associated protein compacts both host and phage DNA and derepresses H-NS silencing.

Son BPatterson-West JArroyo-Mendoza MRamachandran RIben JRZhu JRao VDimitriadis EKHinton DM

Nucleic Acids Res

2021 Sep 20

Tyrosinase Nanoparticles: Understanding the Melanogenesis Pathway by Isolating the Products of Tyrosinase Enzymatic Reaction.

Varghese PKAbu-Asab MDimitriadis EKDolinska MBMorcos GPSergeev YV

Int J Mol Sci

2021 Jan 13

Mechanical properties of nucleoprotein complexes determined by nanoindentation spectroscopy.

Rakshit TMelters DPDimitriadis EKDalal Y

Nucleus

2020 Dec

Protein Stability and Functional Characterization of Intra-Melanosomal Domain of Human Recombinant Tyrosinase-Related Protein 1.

Dolinska MBYoung KLKassouf CDimitriadis EKWingfield PTSergeev YV

Int J Mol Sci

2020 Jan 03

Intrinsic elasticity of nucleosomes is encoded by histone variants and calibrated by their binding partners.

Melters DPPitman MRakshit TDimitriadis EKBui MPapoian GADalal Y

Proc Natl Acad Sci U S A

2019 Nov 26

Durotaxis by Human Cancer Cells.

DuChez BJDoyle ADDimitriadis EKYamada KM

Biophys J

2019 Feb 19

Membrane-associated human tyrosinase is an enzymatically active monomeric glycoprotein.

Kus NJDolinska MBYoung KLDimitriadis EKWingfield PTSergeev YV

PLoS One

2018

Macrophages Shed Excess Cholesterol in Unique Extracellular Structures Containing Cholesterol Microdomains.

Jin XDimitriadis EKLiu YCombs CAChang JVarsano NStempinski EFlores RJackson SNMuller LWoods ASAddadi LKruth HS

Arterioscler Thromb Vasc Biol

2018 Jul

Microscale mapping of extracellular matrix elasticity of mouse joint cartilage: an approach to extracting bulk elasticity of soft matter with surface roughness.

Chandran PLDimitriadis EKMertz ELHorkay F

Soft Matter

2018 Apr 18

Supramolecular Self-assembly of a Model Hydrogelator: Characterization of Fiber Formation and Morphology.

Gao YNieuwendaal RDimitriadis EKHammouda BDouglas JFXu BHorkay F

Gels

2016 Dec

"DNA Binding Region" of BRCA1 Affects Genetic Stability through modulating the Intra-S-Phase Checkpoint.

Masuda TXu XDimitriadis EKLahusen TDeng CX

Int J Biol Sci

2016

HIV Tat protein and amyloid-β peptide form multifibrillar structures that cause neurotoxicity.

Hategan ABianchet MASteiner JKarnaukhova EMasliah EFields ALee MHDickens AMHaughey NDimitriadis EKNath A

Nat Struct Mol Biol

2017 Apr

A New Noncoding RNA Arranges Bacterial Chromosome Organization.

Qian ZMacvanin MDimitriadis EKHe XZhurkin VAdhya S

mBio

2015 Aug 25

Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network.

Artym VVSwatkoski SMatsumoto KCampbell CBPetrie RJDimitriadis EKLi XMueller SCBugge THGucek MYamada KM

J Cell Biol

2015 Feb 02

Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness.

Furusawa TRochman MTaher LDimitriadis EKNagashima KAnderson SBustin M

Nat Commun

2015 Jan 22

DNA nanoparticles with core-shell morphology.

Chandran PLDimitriadis EKLisziewicz JSperansky VHorkay F

Soft Matter

2014 Oct 14

CENP-A octamers do not confer a reduction in nucleosome height by AFM.

Walkiewicz MPDimitriadis EKDalal Y

Nat Struct Mol Biol

2014 Jan

Production and characterization of novel recombinant adeno-associated virus replicative-form genomes: a eukaryotic source of DNA for gene transfer.

Li LDimitriadis EKYang YLi JYuan ZQiao CBeley CSmith RHGarcia LKotin RM

PLoS One

2013

The CENP-A nucleosome: a battle between Dr Jekyll and Mr Hyde.

Bui MWalkiewicz MPDimitriadis EKDalal Y

Nucleus

2013

Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo.

Bui MDimitriadis EKHoischen CAn EQuénet DGiebe SNita-Lazar ADiekmann SDalal Y

Cell

2012 Jul 20

The linker of the interferon response factor 3 transcription factor is not unfolded.

Shukla HVaitiekunas PMajumdar AKDragan AIDimitriadis EKKotova SCrane-Robinson CPrivalov PL

Biochemistry

2012 Aug 14

Galactose repressor mediated intersegmental chromosomal connections in Escherichia coli.

Qian ZDimitriadis EKEdgar REswaramoorthy PAdhya S

Proc Natl Acad Sci U S A

2012 Jul 10

Measurement of plasma volume using fluorescent silica-based nanoparticles.

Eisner COw HYang TJia ZDimitriadis ELi LWang KBriggs JLevine MSchnermann JEspey MG

J Appl Physiol (1985)

2012 Feb

Probing Interactions between Aggrecan and Mica Surface by the Atomic Force Microscopy.

Chandran PLDimitriadis EKBasser PJHorkay F

J Polym Sci B Polym Phys

2010 Dec 15

Tetrameric organization of vertebrate centromeric nucleosomes.

Dimitriadis EKWeber CGill RKDiekmann SDalal Y

Proc Natl Acad Sci U S A

2010 Nov 23

Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the presence of Ca2+: an atomic force microscopy study.

Kotova SVijayasarathy CDimitriadis EKIkonomou LJaffe HSieving PA

Biochemistry

2010 Aug 24

Nucleoprotein intermediates in HIV-1 DNA integration visualized by atomic force microscopy.

Kotova SLi MDimitriadis EKCraigie R

J Mol Biol

2010 Jun 11

Organization of membrane motor in outer hair cells: an atomic force microscopic study.

Sinha GPSabri FDimitriadis EKIwasa KH

Pflugers Arch

2010 Feb

Initial stages of V(D)J recombination: the organization of RAG1/2 and RSS DNA in the postcleavage complex.

Grundy GJRamón-Maiques SDimitriadis EKKotova SBiertümpfel CHeymann JBSteven ACGellert MYang W

Mol Cell

2009 Jul 31

Spherical indentation of soft matter beyond the Hertzian regime: numerical and experimental validation of hyperelastic models.

Lin DCShreiber DIDimitriadis EKHorkay F

Biomech Model Mechanobiol

2009 Oct

The influence of cochlear shape on low-frequency hearing.

Manoussaki DChadwick RSKetten DRArruda JDimitriadis EKO'Malley JT

Proc Natl Acad Sci U S A

2008 Apr 22

Robust strategies for automated AFM force curve analysis-II: adhesion-influenced indentation of soft, elastic materials.

Lin DCDimitriadis EKHorkay F

J Biomech Eng

2007 Dec

Robust strategies for automated AFM force curve analysis--I. Non-adhesive indentation of soft, inhomogeneous materials.

Lin DCDimitriadis EKHorkay F

J Biomech Eng

2007 Jun

Right-handed DNA supercoiling by an octameric form of histone-like protein HU: modulation of cellular transcription.

Kar SChoi EJGuo FDimitriadis EKKotova SLAdhya S

J Biol Chem

2006 Dec 29

Gal repressor-operator-HU ternary complex: pathway of repressosome formation.

Roy SDimitriadis EKKar SGeanacopoulos MLewis MSAdhya S

Biochemistry

2005 Apr 12

Evidence and implications of inhomogeneity in tectorial membrane elasticity.

Shoelson BDimitriadis EKCai HKachar BChadwick RS

Biophys J

2004 Oct

Cytochrome c adsorption to supported, anionic lipid bilayers studied via atomic force microscopy.

Choi EJDimitriadis EK

Biophys J

2004 Nov

Determination of elastic moduli of thin layers of soft material using the atomic force microscope.

Dimitriadis EKHorkay FMaresca JKachar BChadwick RS

Biophys J

2002 May

Arterial wall properties and Womersley flow in Fabry disease.

Moore DFAltarescu GPursley RCampia UPanza JADimitriadis ESchiffmann R

BMC Cardiovasc Disord

2002

Scanning Probe Microscopy Unit

Lab Resources

Atomic Force Imaging and Spectroscopy

Staff

Publications