Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device

2004 ◽  
Vol 287 (5) ◽  
pp. C1184-C1191 ◽  
Author(s):  
Shaohua Hu ◽  
Luc Eberhard ◽  
Jianxin Chen ◽  
J. Christopher Love ◽  
James P. Butler ◽  
...  
Keyword(s):  
Magnetic Beads ◽  
Three Dimensional ◽  
Magnetic Bead ◽  
Mechanical Anisotropy ◽  
Stress Fibers ◽  
Structural Basis ◽  
Mechanical Stiffness ◽  
Cytoskeletal Tension ◽  
Coated Surface ◽  
Deformation Patterns

We describe a three-dimensional magnetic twisting device that is useful in characterizing the mechanical properties of cells. With the use of three pairs of orthogonally aligned coils, oscillatory mechanical torque was applied to magnetic beads about any chosen axis. Frequencies up to 1 kHz could be attained. Cell deformation was measured in response to torque applied via an RGD-coated, surface-bound magnetic bead. In both unpatterned and micropatterned elongated cells on extracellular matrix, the mechanical stiffness transverse to the long axis of the cell was less than half that parallel to the long axis. Elongated cells on poly-l-lysine lost stress fibers and exhibited little mechanical anisotropy; disrupting the actin cytoskeleton or decreasing cytoskeletal tension substantially decreased the anisotropy. These results suggest that mechanical anisotropy originates from intrinsic cytoskeletal tension within the stress fibers. Deformation patterns of the cytoskeleton and the nucleolus were sensitive to loading direction, suggesting anisotropic mechanical signaling. This technology may be useful for elucidating the structural basis of mechanotransduction.

Electron Microscopy and image reconstruction reveal the structural basis for spectrin's elastic properties

1992 ◽  
Vol 50 (1) ◽  
pp. 510-511
Author(s):  
Amy M. McGough ◽  
Robert Josephs
Keyword(s):  
Electron Microscopy ◽  
Elastic Properties ◽  
Conformational Changes ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Membrane Skeleton ◽  
Projection Algorithm ◽  
Structural Basis ◽  
Iterative Approximation ◽  
Membrane Skeletons

The remarkable deformability of the erythrocyte derives in large part from the elastic properties of spectrin, the major component of the membrane skeleton. It is generally accepted that spectrin's elasticity arises from marked conformational changes which include variations in its overall length (1). In this work the structure of spectrin in partially expanded membrane skeletons was studied by electron microscopy to determine the molecular basis for spectrin's elastic properties. Spectrin molecules were analysed with respect to three features: length, conformation, and quaternary structure. The results of these studies lead to a model of how spectrin mediates the elastic deformation of the erythrocyte.Membrane skeletons were isolated from erythrocyte membrane ghosts, negatively stained, and examined by transmission electron microscopy (2). Particle lengths and end-to-end distances were measured from enlarged prints using the computer program MACMEASURE. Spectrin conformation (straightness) was assessed by calculating the particles’ correlation length by iterative approximation (3). Digitised spectrin images were correlation averaged or Fourier filtered to improve their signal-to-noise ratios. Three-dimensional reconstructions were performed using a suite of programs which were based on the filtered back-projection algorithm and executed on a cluster of Microvax 3200 workstations (4).

Construction of plastic contact deformation maps on ceramics: a case study on aluminum nitride

1996 ◽  
Vol 54 ◽  
pp. 636-637
Author(s):  
D. L. Callahan
Keyword(s):  
Plastic Deformation ◽  
Aluminum Nitride ◽  
Mechanical Response ◽  
Three Dimensional ◽  
Bright Field Image ◽  
Perfectly Plastic ◽  
Contrast Analysis ◽  
Deformation Patterns

Modern polishing, precision machining and microindentation techniques allow the processing and mechanical characterization of ceramics at nanometric scales and within entirely plastic deformation regimes. The mechanical response of most ceramics to such highly constrained contact is not predictable from macroscopic properties and the microstructural deformation patterns have proven difficult to characterize by the application of any individual technique. In this study, TEM techniques of contrast analysis and CBED are combined with stereographic analysis to construct a three-dimensional microstructure deformation map of the surface of a perfectly plastic microindentation on macroscopically brittle aluminum nitride.The bright field image in Figure 1 shows a lg Vickers microindentation contained within a single AlN grain far from any boundaries. High densities of dislocations are evident, particularly near facet edges but are not individually resolvable. The prominent bend contours also indicate the severity of plastic deformation. Figure 2 is a selected area diffraction pattern covering the entire indentation area.

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

scholarly journals Structural Insight into African Swine Fever Virus A179L-Mediated Inhibition of Apoptosis

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Suresh Banjara ◽  
Sofia Caria ◽  
Linda K. Dixon ◽  
Mark G. Hinds ◽  
Marc Kvansakul
Keyword(s):  
Crystal Structures ◽  
African Swine Fever Virus ◽  
Three Dimensional ◽  
African Swine Fever ◽  
Fever Virus ◽  
Structural Basis ◽  
Dna Virus ◽  
Content Type ◽  
Antiapoptotic Proteins ◽  
Apoptosis Inhibition

ABSTRACT Programmed cell death is a tightly controlled process critical for the removal of damaged or infected cells. Pro- and antiapoptotic proteins of the Bcl-2 family are pivotal mediators of this process. African swine fever virus (ASFV) is a large DNA virus, the only member of the Asfarviridae family, and harbors A179L, a putative Bcl-2 like protein. A179L has been shown to bind to several proapoptotic Bcl-2 proteins; however, the hierarchy of binding and the structural basis for apoptosis inhibition are currently not understood. We systematically evaluated the ability of A179L to bind proapoptotic Bcl-2 family members and show that A179L is the first antiapoptotic Bcl-2 protein to bind to all major death-inducing mammalian Bcl-2 proteins. We then defined the structural basis for apoptosis inhibition of A179L by determining the crystal structures of A179L bound to both Bid and Bax BH3 motifs. Our findings provide a mechanistic understanding for the potent antiapoptotic activity of A179L by identifying it as the first panprodeath Bcl-2 binder and serve as a platform for more-detailed investigations into the role of A179L during ASFV infection. IMPORTANCE Numerous viruses have acquired strategies to subvert apoptosis by encoding proteins capable of sequestering proapoptotic host proteins. African swine fever virus (ASFV), a large DNA virus and the only member of the Asfarviridae family, encodes the protein A179L, which functions to prevent apoptosis. We show that A179L is unusual among antiapoptotic Bcl-2 proteins in being able to physically bind to all core death-inducing mammalian Bcl-2 proteins. Currently, little is known regarding the molecular interactions between A179L and the proapoptotic Bcl-2 members. Using the crystal structures of A179L bound to two of the identified proapoptotic Bcl-2 proteins, Bid and Bax, we now provide a three-dimensional (3D) view of how A179L sequesters host proapoptotic proteins, which is crucial for subverting premature host cell apoptosis.

scholarly journals An anthropomorphic soft skeleton hand exploiting conditional models for piano playing

2018 ◽  
Vol 3 (25) ◽  
pp. eaau3098 ◽  
Author(s):  
J. A. E. Hughes ◽  
P. Maiolino ◽  
F. Iida
Keyword(s):  
Three Dimensional ◽  
Piano Music ◽  
Robotic Manipulators ◽  
Mechanical Stiffness ◽  
Dynamic Interactions ◽  
Conditional Model ◽  
Three Dimensional Printing ◽  
Behavioral Diversity ◽  
Research Challenge ◽  
Dimensional Printing

The development of robotic manipulators and hands that show dexterity, adaptability, and subtle behavior comparable to human hands is an unsolved research challenge. In this article, we considered the passive dynamics of mechanically complex systems, such as a skeleton hand, as an approach to improving adaptability, dexterity, and richness of behavioral diversity of such robotic manipulators. With the use of state-of-the-art multimaterial three-dimensional printing technologies, it is possible to design and construct complex passive structures, namely, a complex anthropomorphic skeleton hand that shows anisotropic mechanical stiffness. We introduce a concept, termed the “conditional model,” that exploits the anisotropic stiffness of complex soft-rigid hybrid systems. In this approach, the physical configuration, environment conditions, and conditional actuation (applied actuation) resulted in an observable conditional model, allowing joint actuation through passivity-based dynamic interactions. The conditional model approach allowed the physical configuration and actuation to be altered, enabling a single skeleton hand to perform three different phrases of piano music with varying styles and forms and facilitating improved dynamic behaviors and interactions with the piano over those achievable with a rigid end effector.

The Research of a New Method for Manipulating Magnetic Beads through Multi-Layered Flat Micro-Coils Coupled with Permanent Magnet

2013 ◽  
Vol 753-755 ◽  
pp. 1571-1575
Author(s):  
Zhi Hua Liu ◽  
Yu Feng Huang ◽  
Jian Peng Li ◽  
Xin Wei Xu
Keyword(s):  
Magnetic Field ◽  
Permanent Magnet ◽  
Flow Velocity ◽  
Magnetic Beads ◽  
Magnetic Bead ◽  
New Method ◽  
Viscous Resistance ◽  
Main Factors ◽  
The Magnetic Field

Magnetic bead droplet's non-contacted manipulation can be realized in Electromagnetic MEMS, but how to achieve magnetic beads manipulation is the major problem. A new method of multi-layered flat coils coupled with permanent magnet was proposed. Firstly, the theory of magnetic bead manipulation was analyzed and the main factors affected the magnetic beads manipulation was identified; then the magnetic field of multi-layered flat coils and Stokes viscous resistance of magnetic beads were analyzed and simulated quantificationally; finally the magnetic bead capture area was got under different flow velocity. Consequently the feasibility and correctness of this method was verified.

scholarly journals The Magnetic Bead Computing Model of the 0-1 Integer Programming Problem Based on DNA Cycle Hybridization

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Rujie Xu ◽  
Zhixiang Yin ◽  
Zhen Tang ◽  
Jing Yang ◽  
Jianzhong Cui ◽  
...  
Keyword(s):  
Integer Programming ◽  
Programming Problem ◽  
Magnetic Beads ◽  
Specific Binding ◽  
Optimal Solution ◽  
High Sensitivity ◽  
Magnetic Bead ◽  
Integer Programming Problem ◽  
Computing Model ◽  
Dna Strands

Magnetic beads and magnetic Raman technology substrates have good magnetic response ability and surface-enhanced Raman technology (SERS) activity. Therefore, magnetic beads exhibit high sensitivity in SERS detection. In this paper, DNA cycle hybridization and magnetic bead models are combined to solve 0-1 integer programming problems. First, the model maps the variables to DNA strands with hairpin structures and weights them by the number of hairpin DNA strands. This result can be displayed by the specific binding of streptavidin and biotin. Second, the constraint condition of the 0-1 integer programming problem can be accomplished by detecting the signal intensity of the biological barcode to find the optimal solution. Finally, this model can be used to solve the general 0-1 integer programming problem and has more extensive applications than the previous DNA computing model.

scholarly journals Structural basis for the coiled-coil architecture of human CtIP

2021 ◽  
Author(s):  
C. R. Morton ◽  
N. J. Rzechorzek ◽  
J. D. Maman ◽  
M. Kuramochi ◽  
H. Sekiguchi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Coiled Coil ◽  
Strand Break ◽  
Structural Basis ◽  
Binding Motif ◽  
Chromosomal Dna ◽  
Dsb Repair ◽  
Critical Function ◽  
X Ray

AbstractThe DNA repair factor CtIP has a critical function in Double-Strand Break (DSB) repair by Homologous Recombination, promoting the assembly of the repair apparatus at DNA ends and participating in DNA-end resection. However, the molecular mechanisms of CtIP function in DSB repair remain unclear. Here we present an atomic model for the three-dimensional architecture of human CtIP, derived from a multi-disciplinary approach that includes X-ray crystallography, Small-angle X-ray Scattering (SAXS) and Diffracted X-ray Tracking (DXT). Our data show that CtIP adopts an extended dimer-of-dimers structure, in agreement with a role in bridging distant sites on chromosomal DNA during recombinational repair. The zinc-binding motif in CtIP’s N-terminus alters dynamically the coiled coil structure, with functional implications for the long-range interactions of CtIP with DNA. Our results provide a structural basis for the three-dimensional arrangement of chains in the CtIP tetramer, a key aspect of CtIP function in DNA DSB repair.

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