Recruit­ing bac­teria to be tech­no­logy innov­a­tion partners

For most people biofilms con­jure up images of slip­pery stones in a stre­ambed and dirty drains. While there are plenty of ​“bad” biofilms around – they even cause pesky dent­al plaque and a host of oth­er more ser­i­ous med­ic­al prob­lems – a team at the Wyss Insti­tute for Bio­lo­gic­ally Inspired Engin­eer­ing at Har­vard Uni­ver­sity sees biofilms as a robust new plat­form for design­er nan­o­ma­ter­i­als that could clean up pol­luted rivers, man­u­fac­ture phar­ma­ceut­ic­al products, fab­ric­ate new tex­tiles, and more. In short, they want to give biofilms a facelift, and have developed a nov­el pro­tein engin­eer­ing sys­tem called BIND to do so. Using BIND, which stands for Biofilm-Integ­rated Nan­ofiber Dis­play, the team said biofilms could be tomor­row’s liv­ing foundries for the large-scale pro­duc­tion of bio­ma­ter­i­als that can be pro­grammed to provide func­tions not pos­sible with exist­ing mater­i­als. They have repor­ted the proof-of-concept in Nature Com­mu­nic­a­tions. ​“Most biofilm-related research today focuses on how to get rid of biofilms, but we demon­strate here that we can engin­eer these super tough nat­ur­al mater­i­als to per­form spe­cif­ic func­tions — so we may want them around in spe­cif­ic quant­it­ies and for spe­cif­ic applic­a­tions,” said Wyss Insti­tute Core Fac­ulty mem­ber Neel Joshi, Ph.D., the study’s seni­or author. Joshi is also an Asso­ci­ate Pro­fess­or of Chem­ic­al and Bio­lo­gic­al Engin­eer­ing at the Har­vard School of Engin­eer­ing and Applied Sci­ences (SEAS). Biofilms also self-assemble and self-heal. ​“If they get dam­aged, they grow right back because they are liv­ing tis­sues,” said lead author Peter Nguy­en, Ph.D., a Postdoc­tor­al Fel­low at the Wyss Insti­tute and Har­vard SEAS. Biofilms are com­munit­ies of bac­teria ensconced in a slimy, but extremely tough, mat­rix of extra­cel­lu­lar mater­i­al com­posed of sug­ars, pro­teins, genet­ic mater­i­al and more. Dur­ing biofilm form­a­tion indi­vidu­al bac­teria pump out pro­teins that self-assemble out­side the cell – cre­at­ing tangled net­works of fibers that essen­tially glue the cells togeth­er into com­munit­ies that keep the bac­teria safer than they would be on their own. Interest in biofilm engin­eer­ing is skyrock­et­ing, and while sev­er­al oth­er teams have recently developed genet­ic tools to con­trol biofilm form­a­tion, Joshi’s team altered the com­pos­i­tion of the extra­cel­lu­lar mater­i­al itself – essen­tially turn­ing it into a self-rep­lic­at­ing pro­duc­tion plat­form to churn out whatever mater­i­al they wish to pro­duce. ​“Until recently there was not enough cooper­a­tion between syn­thet­ic bio­lo­gists and bio­ma­ter­i­als research­ers to exploit the syn­thet­ic poten­tial of biofilms this way. We are try­ing to bridge that gap,” Joshi said. The team genet­ic­ally fused a pro­tein with a par­tic­u­lar desired func­tion – for example, one known to adhere to steel – onto a small pro­tein called CsgA that is already pro­duced by E. coli bac­teria. The appen­ded domain then went along for the ride through the nat­ur­al pro­cess by which CsgA gets secreted out­side the cell, where it self – assembled into super­tough pro­teins called amyl­oid nan­ofibers. These amyl­oid pro­teins retained the func­tion­al­ity of the added pro­tein – ensur­ing in this case that the biofilm adhered to steel. Amyl­oid pro­teins tra­di­tion­ally get a bad rap for their role in caus­ing tre­mend­ous health chal­lenges such as Alzheimer­’s dis­ease, but in this case their role is fun­da­ment­al to mak­ing BIND so robust. These amyl­oids can spon­tan­eously assemble into fibers that, by weight, are stronger than steel and stiffer than silk. ​“We are excited about the ver­sat­il­ity of the meth­od, too,” Joshi said. The team demon­strated an abil­ity to fuse 12 dif­fer­ent pro­teins to the CsgA pro­tein, with widely vary­ing sequences and lengths. This means in prin­ciple that they can use this tech­no­logy to dis­play vir­tu­ally any pro­tein sequence – a sig­ni­fic­ant fea­ture because pro­teins per­form an array of impress­ive func­tions from bind­ing to for­eign particles to car­ry­ing out chem­ic­al reac­tions, trans­mit­ting sig­nals, provid­ing struc­tur­al sup­port, and trans­port­ing or stor­ing cer­tain molecules. Not only can these func­tions be pro­grammed into the biofilm one at a time, but they can be com­bined to cre­ate mul­ti­func­tion­al biofilms as well. The concept of the micro­bi­al fact­ory is not a new one, but for the first time it is being applied to mater­i­als, as opposed to sol­uble molecules like drugs or fuels. ​“We are essen­tially pro­gram­ming the cells to be fab­ric­a­tion plants,” Joshi said. ​“They don’t just pro­duce a raw mater­i­al as a build­ing block, they orches­trate the assembly of those blocks into high­er order struc­tures and main­tain that struc­ture over time.” ​“The found­a­tion­al work Neel and his team are doing with biofilms offers a glimpse into a much more envir­on­ment­ally sus­tain­able future where gar­gan­tu­an factor­ies are reduced to the size of a cell that we can pro­gram to man­u­fac­ture new mater­i­als that meet our every­day needs – from tex­tiles to energy and envir­on­ment­al clean – up,” said Wyss Insti­tute Found­ing Dir­ect­or Don Ing­ber, M.D., Ph.D. For now the team has demon­strated the abil­ity to pro­gram E. coli biofilms that stick to cer­tain sub­strates, such as steel, oth­ers that can immob­il­ize an array of pro­teins or pro­mote the tem­plat­ing of sil­ver for con­struc­tion of nanowires. This work was primar­ily fun­ded by the Wyss Insti­tute for Bio­lo­gic­ally Inspired Engin­eer­ing at Har­vard Uni­ver­sity. The authors also acknow­ledge sup­port from the Nation­al Sci­ence Found­a­tion Gradu­ate Research Fel­low­ship and the A*STAR Nation­al Sci­ence Gradu­ate Fel­low­ship.

About the Wyss Insti­tute for Bio­lo­gic­ally Inspired Engin­eer­ing at Har­vard University

The Wyss Insti­tute for Bio­lo­gic­ally Inspired Engin­eer­ing at Har­vard Uni­ver­sity uses Nature’s design prin­ciples to devel­op bioin­spired mater­i­als and devices that will trans­form medi­cine and cre­ate a more sus­tain­able world. Work­ing as an alli­ance among all of Har­vard’s Schools, and in part­ner­ship with Beth Israel Dea­con­ess Med­ic­al Cen­ter, Brigham and Women’s Hos­pit­al, Boston Chil­dren’s Hos­pit­al, Dana Farber Can­cer Insti­tute, Mas­sachu­setts Gen­er­al Hos­pit­al, the Uni­ver­sity of Mas­sachu­setts Med­ic­al School, Spauld­ing Rehab­il­it­a­tion Hos­pit­al, Boston Uni­ver­sity, Tufts Uni­ver­sity, and Char­ité — Uni­versitätsmed­iz­in Ber­lin, and the Uni­ver­sity of Zurich, the Insti­tute crosses dis­cip­lin­ary and insti­tu­tion­al bar­ri­ers to engage in high-risk research that leads to trans­form­at­ive tech­no­lo­gic­al break­throughs. By emu­lat­ing Nature’s prin­ciples for self-organ­iz­ing and self-reg­u­lat­ing, Wyss research­ers are devel­op­ing innov­at­ive new engin­eer­ing solu­tions for health­care, energy, archi­tec­ture, robot­ics, and man­u­fac­tur­ing. These tech­no­lo­gies are trans­lated into com­mer­cial products and ther­apies through col­lab­or­a­tions with clin­ic­al invest­ig­at­ors, cor­por­ate alli­ances, and new start-ups.

About the Har­vard School of Engin­eer­ing and Applied Sciences

The Har­vard School of Engin­eer­ing and Applied Sci­ences (SEAS) serves as the con­nect­or and integ­rat­or of Har­vard’s teach­ing and research efforts in engin­eer­ing, applied sci­ences, and tech­no­logy. Through col­lab­or­a­tion with research­ers from all parts of Har­vard, oth­er uni­ver­sit­ies, and cor­por­ate and found­a­tion­al part­ners, we bring dis­cov­ery and innov­a­tion dir­ectly to bear on improv­ing human life and soci­ety. Source: Wyss Insti­tute for Bio­lo­gic­ally Inspired Engin­eer­ing at Har­vard University