Tuning Polymer Hydrophilicity to Regulate Gel Mechanics and Encapsulated Cell Morphology.
Tuning Polymer Hydrophilicity to Regulate Gel Mechanics and Encapsulated Cell Morphology.
复制标题
调节聚合物亲水性以调节凝胶力学和包封细胞形态。
DOI：
10.1002/adhm.202200011
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发表时间：
2022-07
影响因子：
10
通讯作者：
Heilshorn, Sarah C.
中科院分区：
文献类型：
--
作者：
Navarro, Renato S.;Huang, Michelle S.;Roth, Julien G.;Hubka, Kelsea M.;Long, Chris M.;Enejder, Annika;Heilshorn, Sarah C.
关键词：
机械可调的水凝胶是三维细胞培养的有吸引力的平台，因为水凝胶刚度在细胞行为中起重要作用。传统上，水凝胶硬度是通过改变聚合物浓度或交联剂反应基团之间的化学计量来控制的。在这里，我们提出了一种替代策略的基础上调整弹性蛋白样蛋白（ELP）的亲水性。ELP经历相变，导致蛋白质在升高的温度下聚集。我们假设，通过与具有增加的亲水性的含叠氮化物的分子的生物缀合来增加该转变温度将允许通过使交联基团更易接近来直接控制所得凝胶刚度。这些叠氮化物改性的ELP使用生物正交点击化学与双环壬基酮改性的透明质酸（HA-BCN）交联成水凝胶，产生具有可调储能模量（100- 1，000 Pa）的水凝胶。观察到人间充质基质细胞、人脐静脉内皮细胞和人神经祖细胞在包封在不同硬度的水凝胶内时均改变其细胞形态。总之，我们证明了使用蛋白质亲水性作为杠杆来调节水凝胶的机械性能。这些水凝胶在与软组织相关的刚度范围内具有可调模量，支持包封细胞的活力，并由于凝胶刚度而改变细胞铺展。基质硬度是影响细胞表型的关键因素，因此是生物材料设计中的重要变量。我们展示了一种新的策略，通过调节蛋白质的亲水性来控制蛋白质工程生物材料的刚度。这种策略允许合成储能模量范围为100- 1，000 Pa的凝胶，从而导致各种细胞类型的可变细胞铺展。
Mechanically tunable hydrogels are attractive platforms for three-dimensional cell culture, as hydrogel stiffness plays an important role in cell behavior. Traditionally, hydrogel stiffness has been controlled through altering either the polymer concentration or the stoichiometry between crosslinker reactive groups. Here, we present an alternative strategy based upon tuning the hydrophilicity of an elastin-like protein (ELP). ELPs undergo a phase transition that leads to protein aggregation at increasing temperatures. We hypothesize that increasing this transition temperature through bioconjugation with azide-containing molecules of increasing hydrophilicity will allow direct control of the resulting gel stiffness by making the crosslinking groups more accessible. These azide-modified ELPs are crosslinked into hydrogels with bicyclononyne-modified hyaluronic acid (HA-BCN) using bioorthogonal, click chemistry, resulting in hydrogels with tunable storage moduli (100–1,000 Pa). Human mesenchymal stromal cells, human umbilical vein endothelial cells, and human neural progenitor cells are all observed to alter their cell morphology when encapsulated within hydrogels of varying stiffness. Taken together, we demonstrate the use of protein hydrophilicity as a lever to tune hydrogel mechanical properties. These hydrogels have tunable moduli over a stiffness range relevant to soft tissues, support the viability of encapsulated cells, and modify cell spreading as a consequence of gel stiffness. Matrix stiffness is a critical cue that affects cell phenotype and hence is an important variable in biomaterials design. We demonstrate a novel strategy to control the stiffness of protein-engineered biomaterials by tuning protein hydrophilicity. This strategy allowed synthesis of gels with storage moduli ranging from 100–1,000 Pa, resulting in variable cell spreading for a variety of cell types.
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影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
3.2
作者：
Catherine, Christy;Oh, Su Jin;Kim, Dong-Myung
通讯作者：
Kim, Dong-Myung
影响因子：
3.3
作者：
Hadjipanayi, E.;Mudera, V.;Brown, R. A.
通讯作者：
Brown, R. A.
影响因子：
14
作者：
Banerjee, Akhilesh;Arha, Manish;Choudhary, Soumitra;Ashton, Randolph S.;Bhatia, Surita R.;Schaffer, David V.;Kane, Ravi S.
通讯作者：
Kane, Ravi S.