Bionanointerfaces

Cells of all types take cues from the surfaces they encounter in their environment. The cells extract any or all of the mechanical, chemical, spatial, and even temporal information from the surface, but which features they read and how they integrate and translate them into specific behavioral responses is still almost a black box. 

Projects

Vascularized self-lubricating surfaces

Fig. 1: Bio-inspired vascularized fouling-release surfaces.
Fig. 2: Bio-inspired vacularized fouling-release surfaces.
Fig. 3: (A) Schematic of the process to make either infused PDMS or vascularized, infused PDMS. For simple infused PDMS (upper row), cured PDMS is placed in a bath of silicone oil which diffuses into the PDMS solid. For vascularized PDMS, the vascular pattern is created before curing. The sample is then infused externally with silicone oil in the same manner as the non-vascularized PDMS, or internally through filling the vascular network, or both. (B) Methods of creating vascular networks within PDMS: 1) An encased network is created using a 3D mold (a) to create the pattern in PDMS (b). The mold is removed from the cured PMDS (c) and the pattern is covered with a second sheet of PDMS (d and e) which is chemically bonded to the pattern using plasma. (i) an image of a 3D leaf vasculature network after encasing. 2) An embedded network is created following the procedures developed by Lewis et al. (citation). (a) A pattern of 20% w/w pluronic F127 gel at 25 °C is embedded in uncured PDMS. (b) The PDMS is allowed to cure, cooled to 4 °C, and the liquid pluronic is evacuated. (c) The channel is refilled with silicone oil. (i) An image of fluorescently dyed PDMS in a hand-drawn sinuous channel, (ii) a hand-drawn leaf-shape network, and (iii) a 3D-printed linear network.
Fig. 6: (A) Surface coverage of biofilm remaining on lubricant-infused PDMS versus glass control surfaces after incubation in and removal from the liquid medium containing C. reinhardtii, D. salina, or N. oculata. For all three species, there was a significant reduction in the amount of biofilm remaining on the SLIPS surfaces (P < 0.05). (B) Images of the substrates used in the analysis.

We have recently developed a technique for fabricating nanostructured surfaces that enables us to choose and independently vary any combination of geometry, spacing, stiffness, and chemistry, and are using it to analyze how surface features direct bacterial assembly, mammalian cell development, and marine invertebrate settlement at a level of systematic detail that was previously not possible.

As our insight into the cell-nanosurface interface develops, the same fabrication technique will enable us to design and construct surfaces that encode instructions for cell behavior for purposes ranging from anti-biofilm coatings to neural chips to organ development scaffolds.

Hashmi B, Zarzar LD, Mammoto T, Jiang A, Aizenberg J, Ingber DE. Developmentally-Inspired Shrink-Wrap Polymers for Mechanical Induction of Tissue Differentiation. Adv. Mater. 2014;26 (20) :3253-3257. Publisher's VersionAbstract
A biologically inspired thermoresponsive polymer has been developed that mechanically induces tooth differentiation in vitro and in vivo by promoting mesenchymal cell compaction as seen in each pore of the scaffold. This normally occurs during the physiological mesenchymal condensation response that triggers tooth formation in the embryo.
Epstein AK, Hong D, Kim P, Aizenberg J. Biofilm attachment reduction on bioinspired, dynamic, microwrinkling surfaces. New J. Phys. 2013;15 :095018. Publisher's VersionAbstract
Most bacteria live in multicellular communities known as biofilms that are adherent to surfaces in our environment, from sea beds to plumbing systems. Biofilms are often associated with clinical infections, nosocomial deaths and industrial damage such as bio-corrosion and clogging of pipes. As mature biofilms are extremely challenging to eradicate once formed, prevention is advantageous over treatment. However, conventional surface chemistry strategies are either generally transient, due to chemical masking, or toxic, as in the case of leaching marine antifouling paints. Inspired by the nonfouling skins of echinoderms and other marine organisms, which possess highly dynamic surface structures that mechanically frustrate bio-attachment, we have developed and tested a synthetic platform based on both uniaxial mechanical strain and buckling-induced elastomer microtopography. Bacterial biofilm attachment to the dynamic substrates was studied under an array of parameters, including strain amplitude and timescale (1–100 mm s−1), surface wrinkle length scale, bacterial species and cell geometry, and growth time. The optimal conditions for achieving up to  ~ 80% Pseudomonas aeruginosa biofilm reduction after 24 h growth and  ~ 60% reduction after 48 h were combinatorially elucidated to occur at 20% strain amplitude, a timescale of less than  ~ 5 min between strain cycles and a topography length scale corresponding to the cell dimension of  ~ 1 μm. Divergent effects on the attachment of P. aeruginosaStaphylococcus aureus and Escherichia coli biofilms showed that the dynamic substrate also provides a new means of species-specific biofilm inhibition, or inversely, selection for a desired type of bacteria, without reliance on any toxic or transient surface chemical treatments.
Friedlander RS, Vlamakis H, Kim P, Khan M, Kolter R, Aizenberg J. Bacterial flagella explore microscale hummocks and hollows to increase adhesion. Proc. Nat. Acad. Sci. 2013;110 (14) :5624-5629. Publisher's VersionAbstract
Biofilms, surface-bound communities of microbes, are economically and medically important due to their pathogenic and obstructive properties. Among the numerous strategies to prevent bacterial adhesion and subsequent biofilm formation, surface topography was recently proposed as a highly nonspecific method that does not rely on small-molecule antibacterial compounds, which promote resistance. Here, we provide a detailed investigation of how the introduction of submicrometer crevices to a surface affects attachment of Escherichia coli. These crevices reduce substrate surface area available to the cell body but increase overall surface area. We have found that, during the first 2 h, adhesion to topographic surfaces is significantly reduced compared with flat controls, but this behavior abruptly reverses to significantly increased adhesion at longer exposures. We show that this reversal coincides with bacterially induced wetting transitions and that flagellar filaments aid in adhesion to these wetted topographic surfaces. We demonstrate that flagella are able to reach into crevices, access additional surface area, and produce a dense, fibrous network. Mutants lacking flagella show comparatively reduced adhesion. By varying substrate crevice sizes, we determine the conditions under which having flagella is most advantageous for adhesion. These findings strongly indicate that, in addition to their role in swimming motility, flagella are involved in attachment and can furthermore act as structural elements, enabling bacteria to overcome unfavorable surface topographies. This work contributes insights for the future design of antifouling surfaces and for improved understanding of bacterial behavior in native, structured environments.
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Clinging to crevices, E. coli thrive, Harvard press release, April 10, 2013.