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A new tool for measuring surface-biomolecule interactions

测量表面生物分子相互作用的新工具

基本信息

批准号：
8823777
负责人：
Kevin W Plaxco
金额：
$ 22.33万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8823777
关键词：
Acute Address Adsorption Amines Amino Acids Behavior Binding Binding Proteins Biocompatible Materials Biological Biological Phenomena Biopolymers Biosensor Biotechnology Cell membrane Charge Chimera organism DNA Development Devices Drug Targeting Electrodes Empirical Research Exhibits Free Energy Gold Health Investigation Ionic Strengths Length Literature Maps Measurement Measures Membrane Proteins Methods Methylene blue Modeling Monitor Nature Nucleic Acid Binding Nucleic Acids Optical reporter Outcome Oxidation-Reduction Peptides Phase Physiologic pulse Protein Microchips Proteins Reporter Research Resistance Site Solutions Structure Surface Techniques Tertiary Protein Structure Testing Thermodynamics Thymine Time Tissue Engineering Urea Validation Variant Work base density design improved inorganic phosphate insight interest migration monolayer nanoparticle novel phosphonate polypeptide predictive modeling programs research study response scaffold stem theories tool

项目摘要

DESCRIPTION (provided by applicant): Why do biomolecules retain activity when attached to some surfaces (e.g., the cell membrane) and yet almost invariably unfold and inactivate when attached to others (e.g., many artificial surfaces)? And how can we recreate the former effect to produce artificial surfaces on which attached biomolecules similarly retain their function? To date our ability to address these important questions has been hampered by an acute lack of quantitative experimental methods for measuring the thermodynamics of biomolecule-surface interactions. That is, despite a large body of qualitative literature describing how adsorption alters biomolecular structure, and a large number of empirical studies searching for adsorption- resistant surfaces, quantitative, experimentally testable insights into how and why this occurs have proven elusive. Thus motivated, we propose here the development and validation of a novel experimental (electrochemical) approach to measuring the folding free energy of biomolecules site-specifically attached to well-defined macroscopic surfaces. Comparison with the folding free energy in bulk solution then informs on the thermodynamics -and thus mechanisms- underlying biopolymer-surface interactions. To date we have employed this approach to characterize the easily modeled folding of a surface-confined DNA stem-loop in studies that have, for the first time, defined experimentally the extent to which, and mechanisms by which a specific biomolecule interacts with a range of well-defined, macroscopic surfaces. Here we propose a two-year research program aimed at adapting this quantitative experimental tool to the study of protein-surface interactions.

描述（由申请人提供）：为什么生物分子在附着于某些表面（例如，细胞膜）并且当附着于其它细胞时几乎总是展开和折叠（例如，许多人造表面）？我们怎样才能重现前一种效果，制造出人造表面，使附着的生物分子同样保持其功能？到目前为止，我们解决这些重要问题的能力受到严重缺乏定量实验方法来测量生物分子表面相互作用的热力学的阻碍。也就是说，尽管大量定性文献描述了吸附如何改变生物分子结构，并且大量实证研究寻找抗吸附表面，但对如何以及为什么发生这种情况的定量的、实验上可测试的见解已被证明是难以捉摸的。因此，出于动机，我们在这里提出了一种新的实验（电化学）的方法来测量生物分子的折叠自由能的发展和验证的站点特异性连接到定义明确的宏观表面。与本体溶液中的折叠自由能的比较，然后通知的热力学-从而机制-生物聚合物表面相互作用的基础。到目前为止，我们已经采用这种方法来表征的表面限制的DNA茎环的研究中，第一次，实验定义的程度，和机制，一个特定的生物分子相互作用的范围内明确定义的，宏观表面的折叠容易建模。在这里，我们提出了一个为期两年的研究计划，旨在适应这种定量的实验工具，蛋白质表面相互作用的研究。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Experimental Measurement of Surface Charge Effects on the Stability of a Surface-Bound Biopolymer.

表面电荷对表面结合生物聚合物稳定性影响的实验测量。

DOI：
10.1021/acs.langmuir.8b01004
发表时间：
2018
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
0
作者：
Watkins,HerschelM;Ricci,Francesco;Plaxco,KevinW
通讯作者：
Plaxco,KevinW

Quantitative measurements of protein-surface interaction thermodynamics.

蛋白质-表面相互作用热力学的定量测量。

DOI：
10.1073/pnas.1800287115
发表时间：
2018
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Kurnik,Martin;Ortega,Gabriel;Dauphin-Ducharme,Philippe;Li,Hui;Caceres,Amanda;Plaxco,KevinW
通讯作者：
Plaxco,KevinW

Effects of crowding on the stability of a surface-tethered biopolymer: an experimental study of folding in a highly crowded regime.