Use of adhesion molecules as bond stress-enhanced nanoscale binding switches
First Claim
1. A method for changing binding strength of an isolated force-activated bond stress-dependent adhesion molecule (I-FABSDAM) to a force-activated bond stress-dependent binding ligand (FABSDB-L) for said I-FABSDAM, said method comprising changing a bond stress on said I-FABSDAM wherein said binding strength increases when said bond stress increases and decreases when said bond stress decreases.
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Accused Products
Abstract
Methods, compositions and devices are provided based on changing the binding strength of an adhesion molecule to a ligand by changing the force exerted on the bound complex between adhesion molecule and ligand, for example by changing the shear stress acting on the complex. The adhesion molecules and their ligands of this invention bind more tightly when a force-activated bond stress, such as shear force, applied to the adhesion molecules is increased, and bond less tightly when the stress is decreased. The adhesion molecules can be isolated from their sources in nature or can remain attached to their natural sources. They can be engineered, e.g., by altering their amino acid sequences or by binding to antibodies or other particles, to alter their binding properties. They can be attached to a wide range of substrates including particles and device surfaces to form adhesive systems which are capable of sticking to other particles and/or device surfaces to which ligands for the adhesion molecules have been attached. The adhesion molecules and ligands described herein can be used to control binding and release of components of an adhesive system by increasing or decreasing the force-activated bond stresses applied to the adhesion molecules.
68 Citations
85 Claims
- 1. A method for changing binding strength of an isolated force-activated bond stress-dependent adhesion molecule (I-FABSDAM) to a force-activated bond stress-dependent binding ligand (FABSDB-L) for said I-FABSDAM, said method comprising changing a bond stress on said I-FABSDAM wherein said binding strength increases when said bond stress increases and decreases when said bond stress decreases.
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43. A method for removing a target particle from a fluid comprising:
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(a) adding to said fluid a target particle binding agent, said target particle binding agent being attached to a first member of a FABSDAM/FABSDB-L pair;
(b) adding to said fluid the second member of a FABSDAM/FABSDB-L pair attached to a removing agent;
(c) allowing said target particle binding agent to bind said target particle;
(d) applying a bond stress to said FABSDAM to allow force-activated bond stress-dependent binding of said first pair member and said second pair member, thereby forming a complex comprising said target particle, said target particle binding agent attached to said first pair member, and said second pair member attached to said removing agent; and
(e) removing said complex from said fluid. - View Dependent Claims (44, 45, 46, 49, 50)
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47. A method for separating first FABSDB-Ls from second FABSDB-Ls, wherein said FABSDB-Ls are in a fluid, wherein said FABSDB-Ls are capable of binding to FABSDAMs in a force-activated bond stress-dependent manner, and wherein said first and second FABSDB-Ls induce different bond stresses on said FABSDAM under the same conditions, said method comprising:
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(a) contacting said fluid with an amount of said FABSDAMs sufficient to bind substantially all of said first FABSDB-Ls, wherein said FABSDAMs are attached to a removing agent;
(b) applying a bond stress to said FABSDAMs sufficient to cause binding of said first FABSDB-Ls to said FABSDAMs to form a complex, said bond stress being insufficient to cause binding of said second FABSDB-Ls to said FABSDAMs; and
(c) removing said complex comprising said first FABSDB-Ls, and FABSDAMs and said removing agent from said fluid. - View Dependent Claims (48, 51, 52)
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- 53. A fluidic device comprising a surface having a plurality of I-FABSDAMs attached thereto.
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56. A method for selectively releasing into a fluid first FABSDB-Ls from a plurality of FABSDAMs to which first and second FABSDB-Ls are stress-dependently bound, and wherein when said FABSDB-Ls are bound to said FABSDAMs under bond stress, said first and second FABSDB-Ls induce different bond stresses on said FABSDAMs under the same fluid flow conditions, said method comprising:
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(a) contacting said fluid with said FABSDAMs bound to said SDDB-Ls; and
(b) changing the bond stress on said FABSDAMs by an amount sufficient to cause release of said first FABSDB-Ls into said fluid, but insufficient to cause release of said second FABSDB-Ls into said fluid.
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57. A method for selectively concentrating first FABSDB-Ls from second FABSDB-Ls, wherein said FABSDB-Ls are in a fluid, wherein said FABSDB-Ls are capable of binding to FABSDAMs in a force-activated bond stress-dependent manner, and wherein said first and second FABSDB-L induce different bond stresses on said FABSDAM under the same conditions, said method comprising:
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(a) contacting said fluid with an amount of said FABSDAMs sufficient to bind substantially all of said first FABSDB-Ls, wherein said FABSDAMs are attached to a removing agent;
(b) applying a bond stress to said FABSDAMS sufficient to cause binding of said first FABSDB-Ls to said FABSDAMs to form a complex, said bond stress being insufficient to cause binding of said second FABSDB-Ls to said FABSDAMs; and
(c) removing said complex comprising said first FABSDB-Ls and FABSDAMS and said removing agent from said fluid.
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58. A method for measuring the rate of flow of a fluid comprising:
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(a) adding a plurality of FABSDAMs or FABSDB-Ls to said fluid;
(b) placing a plurality of FABSDAMs capable of binding to said FABSDB-Ls or a plurality of FABSDB-Ls capable of binding to said FABSDAMs in contact with said fluid;
(c) allowing said FABSDAMs and said FABSDB-Ls to bind in a force-activated bond stress-dependent manner; and
(d) detecting and quantitatively measuring the amount of binding of said FABSDAMs to said FABSDB-Ls;
wherein said amount of binding is indicative of the rate of flow of said fluid. - View Dependent Claims (59, 60, 61, 62)
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63. A method for delivering a particle to a surface of a system, said surface having attached thereto one member of an I-FABSDAM/FABSDB-L pair, said system also comprising a fluid in contact with said surface, said method comprising:
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(a) adding to said fluid the other member of said pair attached to said particle; and
(b) allowing said pair members to bind in a force-activated bond stress-dependent manner.
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- 64. A bond stress-activated valve for controlling a fluid flow rate in a channel, said channel having a surface in contact with said fluid, said channel surface having attached thereto a plurality of a first member of an I-FABSDAM/FABSDB-L pair, said fluid comprising a plurality of the second member of said pair, wherein said first and second members are present in an amount sufficient to clog or partially clog said channel when bound in complexes in a force-activated bond stress-dependent manner.
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67. A bond stress-activated adhesive system comprising:
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(a) a plurality of I-FABSDAMs; and
(b) a plurality of FABSDB-Ls capable of binding to said I-FABSDAMs in a bond stress dependent manner. - View Dependent Claims (68, 69, 70)
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71. A method for making a bond stress-activated adhesive system comprising:
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(a) attaching a first member of an I-FABSDAM/FABSDB-L pair to a surface of a first film; and
(b) attaching the second member of said pair to a surface of a second film.
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72. A viscosity modifier comprising a plurality of I-FABSDAMs and a plurality of FABSDB-Ls, said I-FABSDAMs and FABSDB-Ls being capable of binding to each other in force-activated bond stress-dependent manner.
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73. A method for modifying the viscosity of a fluid comprising:
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(a) adding to said fluid a plurality of I-FABSDAMs;
(b) adding to said fluid a plurality of FABSDB-Ls capable of binding in a shear stress-dependent manner to said I-FABSDAMs; and
(c) changing a bond stress on said I-FABSDAMs.
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74. A method for interfering with the force-activated bond stress-dependent binding of a FABSDAM and a FABSDB-L capable of binding to said FABSDAM in a force-activated bond stress-dependent manner, said method comprising contacting said FABSDAM with an antibody capable of binding said FABSDAM but incapable of binding to a FABSDB-L-binding domain of said FABSDAM;
- and allowing said antibody to bind said FABSDAM.
- View Dependent Claims (75)
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76. A monoclonal antibody generated using, and capable of binding to, a polypeptide having an amino acid sequence selected from the group consisting of FimH amino acids 25-31 (SEQ ID NO:
- 1), FimH amino acids 110-123 (SEQ ID NO;
2), and FimH amino acids 150-160 (SEQ ID NO;
3).
- 1), FimH amino acids 110-123 (SEQ ID NO;
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77. A polyclonal antibody generated using, and capable of binding to, a polypeptide having an amino acid sequence selected from the group consisting of FimH amino acids 25-31 (SEQ ID NO:
- 1), FimH amino acids 110-123 (SEQ ID NO;
2), and FimH amino acids 150-160 (SEQ ID NO;
3).
- 1), FimH amino acids 110-123 (SEQ ID NO;
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78. An antibody generated using, and capable of binding to, the force-activated structure of a FABSDAM polypeptide.
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79. An immunogenic composition comprising a polypeptide having an amino acid sequence selected from the group consisting of FimH amino acids 25-31 (SEQ ID NO:
- 1), FimH amino acids 110-123 (SEQ ID NO;
2), and FimH amino acids 150-160 (SEQ ID NO;
3). - View Dependent Claims (80)
- 1), FimH amino acids 110-123 (SEQ ID NO;
- 81. A method for making an engineered FimH polypeptide having different force-activated bond stress-dependent binding strength to a selected FABSDB-L than a natural FimH polypeptide, said method comprising engineering a DNA sequence encoding a FimH polypeptide to encode an engineered FimH polypeptide and expressing said engineered FimH polypeptide, wherein said engineered polypeptide comprises an amino acid substitution at an amino acid position selected from positions 154-156, position 32, and position 124,
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84. A FimH polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 1, SEQ ID NO;
2, SEQ ID NO;
3, SEQ ID NO;
4, SEQ ID NO;
5, SEQ ID NO;
6, SEQ ID NO;
7, SEQ ID NO;
8, SEQ ID NO;
9, SEQ ID NO;
10, SEQ ID NO;
l1, and SEQ ID NO;
12.
- 1, SEQ ID NO;
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85. A method for changing binding strength of an isolated force-activated bond stress-dependent adhesion molecule (I-FABSDAM) to a force-activated bond stress-dependent binding ligand (FABSDB-L) for said I-FABSDAM, said method comprising changing a bond stress on said I-FABSDAM;
- wherein said binding strength increases when said bond stress decreases and decreases when said bond stress increases;
wherein said bond stress is between an upper force-activated bond stress-dependent threshold of said I-FABSDAM and a higher force-activated bond stress-dependent binding threshold of said I-FABSDAM.
- wherein said binding strength increases when said bond stress decreases and decreases when said bond stress increases;
Specification