Abstract:
:Antibodies are key tools in biomedical research and medicine. Their binding properties are classically measured in solution and characterized by an affinity. However, in physiological conditions, antibodies can bridge an immune effector cell and an antigen-presenting cell, implying that mechanical forces may apply to the bonds. For example, in antibody-dependent cell cytotoxicity-a major mode of action of therapeutic monoclonal antibodies-the Fab domains bind the antigens on the target cell, whereas the Fc domain binds to the activating receptor CD16 (also known as FcgRIII) of an immune effector cell, in a quasi-bidimensional environment (2D). Therefore, there is a strong need to investigate antigen/antibody binding under force (2D) to better understand and predict antibody activity in vivo. We used two anti-CD16 nanobodies targeting two different epitopes and laminar flow chamber assay to measure the association and dissociation of single bonds formed between microsphere-bound CD16 antigens and surface-bound anti-CD16 nanobodies (or single-domain antibodies), simulating 2D encounters. The two nanobodies exhibit similar 2D association kinetics, characterized by a strong dependence on the molecular encounter duration. However, their 2D dissociation kinetics strongly differ as a function of applied force: one exhibits a slip bond behavior in which off rate increases with force, and the other exhibits a catch-bond behavior in which off rate decreases with force. This is the first time, to our knowledge, that catch-bond behavior was reported for antigen-antibody bond. Quantification of natural killer cells spreading on surfaces coated with the nanobodies provides a comparison between 2D and three-dimensional adhesion in a cellular context, supporting the hypothesis of natural killer cell mechanosensitivity. Our results may also have strong implications for the design of efficient bispecific antibodies for therapeutic applications.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
González C,Chames P,Kerfelec B,Baty D,Robert P,Limozin Ldoi
10.1016/j.bpj.2019.03.012subject
Has Abstractpub_date
2019-04-23 00:00:00pages
1516-1526issue
8eissn
0006-3495issn
1542-0086pii
S0006-3495(19)30198-5journal_volume
116pub_type
杂志文章abstract::The presence of tryptophan residues as intrinsic fluorophores in most proteins makes them an obvious choice for fluorescence spectroscopic analyses of such proteins. Membrane proteins have been reported to have a significantly higher tryptophan content than soluble proteins. The role of tryptophan residues in the stru...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(97)78116-5
更新日期:1997-08-01 00:00:00
abstract::Halorhodopsin (HR), the light-driven chloride transport pigment of Halobacterium halobium, was bleached and reconstituted with retinal analogues with the pi electron system interrupted at different locations (dihydroretinals). The absorption maxima of the artificial pigments formed with the dihydroretinals are found t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(88)83080-7
更新日期:1988-02-01 00:00:00
abstract::The effect of agarose on nucleation of hen egg white lysozyme crystal was examined quantitatively using a temperature-jumping technique. For the first time, to our knowledge, the inhibition of agarose during the nucleation of lysozyme was quantified in two respects: a), the effect of increasing interfacial nucleation ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.108.135574
更新日期:2008-12-15 00:00:00
abstract::The wormlike-chain (WLC) model is widely used to describe the energetics of DNA bending. Motivated by recent experiments, alternative, so-called subelastic chain models were proposed that predict a lower elastic energy of highly bent DNA conformations. Until now, no unambiguous verification of these models has been ob...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2012.05.050
更新日期:2012-07-18 00:00:00
abstract::The thermophilic Bacillus caldolyticus cold shock protein (Bc-Csp) differs from the mesophilic Bacillus subtilis cold shock protein B (Bs-CspB) in 11 of the 66 residues. Stability measurements of Schmid and co-workers have implicated contributions of electrostatic interactions to the thermostability. To further elucid...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)75027-9
更新日期:2003-04-01 00:00:00
abstract::Hemoglobin functions as a tetrameric oxygen transport protein, with each subunit containing a heme cofactor. Its denaturation, either in vivo or in vitro, involves autoxidation to methemoglobin, followed by cofactor loss and globin unfolding. We have proposed a global disassembly scheme for human methemoglobin, linkin...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2020.01.031
更新日期:2020-03-24 00:00:00
abstract::Fluorescence fluctuation spectroscopy has become an important measurement tool for investigating molecular dynamics, molecular interactions, and chemical kinetics in biological systems. Although the basic theory of fluctuation spectroscopy is well established, it is not widely recognized that saturation of the fluores...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.052779
更新日期:2005-09-01 00:00:00
abstract::Verapamil and amlodipine are calcium ion influx inhibitors of wide clinical use. They are partially charged at neutral pH and exhibit amphiphilic properties. The noncharged species can easily cross the lipid membrane. We have measured with solid-state NMR the structural changes induced by verapamil upon incorporation ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.106.089581
更新日期:2006-10-15 00:00:00
abstract::We expressed rod-type homotetrameric cyclic nucleotide-gated (CNGA1) channels in Xenopus oocytes and studied activation by photolysis-induced jumps of the 3',5'-cyclic guanosine monophosphate (cGMP) concentration and by voltage steps. cGMP jumps to increasing concentrations up to the EC50 value of 46.5 microM decelera...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.105.078667
更新日期:2006-05-01 00:00:00
abstract::The spontaneous folding of two Neisseria outer membrane proteins, opacity-associated (Opa)(60) and Opa(50) into lipid vesicles was investigated by systematically varying bulk and membrane properties. Centrifugal fractionation coupled with sodium dodecyl sulfate polyacrylamide gel electrophoresis mobility assays enable...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.03.025
更新日期:2011-05-04 00:00:00
abstract::Omega-3 polyunsaturated fatty acids (n-3 PUFA), enriched in fish oils, are increasingly recognized to have potential benefits for treating many human afflictions. Despite the importance of PUFA, their molecular mechanism of action remains unclear. One emerging hypothesis is that phospholipids containing n-3 PUFA acyl ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2012.06.016
更新日期:2012-07-18 00:00:00
abstract::The axial deformation of a pipette-pressurized fluid membrane bag produces minuscule yet well-defined, reproducible forces. The stiffness of this ultrasensitive force transducer is tunable and largely independent of the constitutive membrane behavior. Based on a rigorous variational treatment, we present both numerica...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.104091
更新日期:2007-07-15 00:00:00
abstract::The switch 1 region of myosin forms a lid over the nucleotide phosphates as part of a structure known as the phosphate-tube. The homologous region in kinesin-family motors is more open, not interacting with the nucleotide. We used molecular dynamics (MD) simulations to examine a possible displacement of switch 1 of th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)76092-4
更新日期:2001-03-01 00:00:00
abstract::Current viral docking models have relied upon the assumption that bond formation and breakage are independent of viral and docking surface geometry, as well as the forces exerted on the bonds. This assumption, known as the equivalent site hypothesis (ESH), is examined in detail using a newly developed simulation techn...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.103.027813
更新日期:2004-06-01 00:00:00
abstract::In the outer hair cell (OHC), the extracisternal space (ECiS) is a conduit and reservoir of the molecular and ionic substrates of the lateral wall, including those necessary for electromotility. To determine the mechanisms through which molecules are transported in the ECiS of the OHC, we selectively imaged the time-d...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.06.011
更新日期:2009-08-19 00:00:00
abstract::An approach is described using fluorescence resonance energy transfer (FRET) to detect inhomogeneity in lipid organization, on distance scales of the order of tens of nanometers or greater, in lipid bilayers. This approach compares the efficiency of energy transfer between two matched fluorescent lipid donors, differi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74542-1
更新日期:2003-08-01 00:00:00
abstract::We accelerate protein folding in all-atom molecular dynamics simulations by introducing alternating hydrogen bond potentials as a supplement to the force field. The alternating hydrogen bond potentials result in accelerated hydrogen bond reordering, which leads to rapid formation of secondary structure elements. The m...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.122192
更新日期:2008-05-15 00:00:00
abstract::Stationary and kinetic experiments were performed on lipid bilayer membranes to study the mechanism of iodine- and bromine-mediated halide transport in detail. The stationary conductance data suggested that four different 1:1 complexes between I2 and Br2 and the halides I- and Br- were responsible for the observed con...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(93)81315-8
更新日期:1993-12-01 00:00:00
abstract::We continue in this paper the presentation of theoretical and experimental methods for the joint refinement of neutron and x-ray lamellar diffraction data for the analysis of fluid (L alpha phase) bilayer structure (Wiener, M. C., and S. H. White. 1991 a, b, c. Biophys. J. 59:162-173 and 174-185; Biochemistry. 30:6997...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(92)81848-9
更新日期:1992-02-01 00:00:00
abstract::Here, we report the first direct observation of Van der Waals' attraction between biomembrane capsules using measurements of the free energy reduction per unit area of membrane-membrane contact formation. In these studies, the membrane capsules were reconstituted neutral (egg phosphatidylcholine) lipid bilayers of gia...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(84)84039-4
更新日期:1984-09-01 00:00:00
abstract::It has been observed in numerical experiments that adding a cargo to a motor protein can regularize its gait. Here we explain these results via asymptotic analysis on a general stochastic motor protein model. This analysis permits a computation of various observables (e.g., the mean velocity) of the motor protein and ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.108.130674
更新日期:2008-09-15 00:00:00
abstract::The depth of insertion of an antimicrobial peptide, protegrin-1 (PG-1), in lipid bilayers is investigated using solid-state NMR. Paramagnetic Mn(2+) ions bind to the surface of lipid bilayers and induce distance-dependent dipolar relaxation of nuclear spins. By comparing the signal dephasing of the peptide with that o...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74660-8
更新日期:2003-10-01 00:00:00
abstract::We have studied the wavelength dependence of retinal Schiff base absorbencies on the protonation state of the chromophore at the multiconfigurational level of theory using second order perturbation theory (CASPT2) within an atomic natural orbital basis set on MP2 optimized geometries. Quantitative agreement between ca...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.106.087122
更新日期:2006-07-01 00:00:00
abstract::In most studied microbial rhodopsins two conserved carboxylic acid residues (the homologs of Asp-85 and Asp-212 in bacteriorhodopsin) and an arginine residue (the homolog of Arg-82) form a complex counterion to the protonated retinylidene Schiff base, and neutralization of the negatively charged carboxylates causes re...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.03.002
更新日期:2014-04-15 00:00:00
abstract::One of the unusual properties of elastin is its ability to coacervate, which has been proposed to play an important role in the alignment of monomeric elastin for cross-linking into the polymeric elastin matrix. The temperature at which this transition takes place depends on several factors including protein concentra...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.110809
更新日期:2007-11-15 00:00:00
abstract::A novel combined approach of molecular dynamics (MD) and Monte Carlo simulations is developed to calculate various free-volume distributions as a function of position in a lipid bilayer membrane at 323 K. The model bilayer consists of 2 x 100 chain molecules with each chain molecule having 15 carbon segments and one h...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(93)81156-1
更新日期:1993-09-01 00:00:00
abstract::Flow dialysis has found widespread use in determining the dissociation constant (KD) of a protein-ligand interaction or the amount of available binding sites (E0). This method has the potency to measure both these parameters in a single experiment and in this article a method to measure simultaneously the KD and E0 is...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(04)74259-9
更新日期:2004-04-01 00:00:00
abstract::We examined four cardiomyopathy-causing mutations of troponin I that appear to disturb function by altering the distribution of thin filament states. The R193H (mouse) troponin I mutant had greater than normal actin-activated myosin-S1 ATPase activity in both the presence and absence of calcium. The rate of ATPase act...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2008.12.3909
更新日期:2009-03-18 00:00:00
abstract::In recent experimental reports, robust circadian oscillation of the phosphorylation level of KaiC has been reconstituted by incubating three cyanobacterial proteins, KaiA, KaiB, and KaiC, with ATP in vitro. This reconstitution indicates that protein-protein interactions and the associated ATP hydrolysis suffice to gen...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.02.036
更新日期:2010-06-02 00:00:00
abstract::The outer membrane (OM) of Gram-negative bacteria is composed of lipopolysaccharide (LPS) in the outer leaflet and phospholipids in the inner leaflet. The outer membrane protein H (OprH) of Pseudomonas aeruginosa provides an increased stability to the OMs by directly interacting with LPS. Here we report the influence ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.12.006
更新日期:2017-01-24 00:00:00