Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury

被引：248

作者：

Alvarez, Z. ^{[1
,2
]}

Kolberg-Edelbrock, A. N. ^{[1
,3
]}

Sasselli, I. R. ^{[1
,4
,9
]}

Ortega, J. A. ^{[1
,5
]}

Qiu, R. ^{[1
,4
]}

Syrgiannis, Z. ^{[1
,4
]}

Mirau, P. A. ^{[6
]}

Chen, F. ^{[1
]}

Chin, S. M. ^{[1
,4
]}

Weigand, S. ^{[7
]}

Kiskinis, E. ^{[1
,5
]}

Stupp, S., I ^{[1
,2
,3
,4
,8
]}

机构：

[1] Northwestern Univ, Simpson Querrey Inst BioNanotechnol, Chicago, IL 60611 USA

[2] Northwestern Univ, Dept Med, Chicago, IL 60611 USA

[3] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA

[4] Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA

[5] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Dept Physiol, Chicago, IL 60611 USA

[6] Air Force Res Labs, Mat & Mfg Directorate, Nanostruct & Biol Mat Branch, Wright Patterson AFB, OH 45433 USA

[7] Northwestern Univ, DuPont Northwestern Dow Collaborat Access Team Sy, DND CAT, Argonne, IL 60439 USA

[8] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA

[9] Basque Res & Technol Alliance BRTA, Ctr Cooperat Res Biomat CIC BiomaGUNE, San Sebastian 20014, Spain

来源：

SCIENCE | 2021年 / 374卷 / 6569期

基金：

美国国家科学基金会;

关键词：

PEPTIDE; NMR; DYNAMICS; MECHANICS; DIFFUSION; PROTEINS; SURFACES; FORCES; CELLS;

D O I：

10.1126/science.abh3602

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor b1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive domains, we intensified the motions of molecules within scaffold fibrils. This resulted in notable differences in vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery. We hypothesize that the signaling of cells by ensembles of molecules could be optimized by tuning their internal motions.

引用

页码：848 / +

页数：74

共 51 条

[1] Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers [J].