C. Hartemink | Massachusetts Institute of Technology (MIT) (original) (raw)

Papers by C. Hartemink

Research paper thumbnail of Structural basis of filamin A functions

The Journal of Cell Biology, 2007

Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. ... more Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that suggests their unfolding may accommodate pre-stress-mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.

Research paper thumbnail of Structural basis of filamin A functions

The Journal of Cell Biology, 2007

Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. ... more Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that suggests their unfolding may accommodate pre-stress-mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.

Research paper thumbnail of Three-dimensional reconstruction of the actin cytoskeleton from stereo images

Journal of Biomechanics, 2000

In eucaryotic cells, actin "laments are abundant components in the cytoskeleton where they form a... more In eucaryotic cells, actin "laments are abundant components in the cytoskeleton where they form a complex three dimensional (3D) structural network that provides the cell with its shape and mechanical properties. However, understanding the structural and mechanical properties of actin "laments composing the cell cytoskeleton is often hampered by the inability to faithfully reconstruct the three-dimensional geometric relationships. This paper presents a vision-based reconstruction approach that automatically reconstitutes the three-dimensional structures of cytoskeletal polymers from stereo image pairs taken at the di!erent tilt angles. The approach "nds corresponding points between two images and recovers the depth information about the structures. The computational process consists of three major procedures: feature representation, stereo matching, and disparity re"nement, implemented in a multi-resolution manner based on a coarse-to-"ne strategy. The reconstruction depicts the three-dimensional structure of cytoskeletal polymers and their geometric relationships. New and useful information becomes available and allows quantitative analysis of the structure. Measurement of the cytoskeleton geometrical properties and the "lament concentration in a de"ned volume are obtained by direct calculation.

Research paper thumbnail of Structural basis of filamin A functions

The Journal of Cell Biology, 2007

Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. ... more Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that suggests their unfolding may accommodate pre-stress-mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.

Research paper thumbnail of Structural basis of filamin A functions

The Journal of Cell Biology, 2007

Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. ... more Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that suggests their unfolding may accommodate pre-stress-mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.

Research paper thumbnail of Structural basis of filamin A functions

The Journal of Cell Biology, 2007

Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. ... more Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that suggests their unfolding may accommodate pre-stress-mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.

Research paper thumbnail of Three-dimensional reconstruction of the actin cytoskeleton from stereo images

Journal of Biomechanics, 2000

In eucaryotic cells, actin "laments are abundant components in the cytoskeleton where they form a... more In eucaryotic cells, actin "laments are abundant components in the cytoskeleton where they form a complex three dimensional (3D) structural network that provides the cell with its shape and mechanical properties. However, understanding the structural and mechanical properties of actin "laments composing the cell cytoskeleton is often hampered by the inability to faithfully reconstruct the three-dimensional geometric relationships. This paper presents a vision-based reconstruction approach that automatically reconstitutes the three-dimensional structures of cytoskeletal polymers from stereo image pairs taken at the di!erent tilt angles. The approach "nds corresponding points between two images and recovers the depth information about the structures. The computational process consists of three major procedures: feature representation, stereo matching, and disparity re"nement, implemented in a multi-resolution manner based on a coarse-to-"ne strategy. The reconstruction depicts the three-dimensional structure of cytoskeletal polymers and their geometric relationships. New and useful information becomes available and allows quantitative analysis of the structure. Measurement of the cytoskeleton geometrical properties and the "lament concentration in a de"ned volume are obtained by direct calculation.

Research paper thumbnail of Structural basis of filamin A functions

The Journal of Cell Biology, 2007

Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. ... more Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that suggests their unfolding may accommodate pre-stress-mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.