INTELLECTUAL MERIT: This program will develop biomaterial surfaces that selectively manipulate bacteria, controlling their adhesion at a level useful for separations, while discriminating and killing targeted types. The surfaces are designed not to harm mammalian cells or accumulate an overcoat of (dead) bacterial debris that can reduce surface activity and support infection. On the surfaces designed and fabricated in this program, the organization of cationic and hydrophobic groups on copolymer chains within antimicrobial polymer brushes will borrow from the membrane-active facially amphiphilic character of host-defense peptides, part of the innate immune system, which evades bacterial resistance. At the 10-300 nm length scale, these new surfaces will emulate the heterogeneous energy landscapes of cell surfaces where rafts cluster proteinaceous functionality to enhance adhesion and signaling. Nano-clustered (10-50 nm) antimicrobial or adhesive functionalities will be randomly distributed on synthetic surfaces whose underlying sterically repulsive character towards cells and bacteria derives from PEG or zwitterionic brushes. These heterogeneous surfaces distinguish bacteria through differences in dynamic adhesion, sensitive to cell size, shape, local curvature, softness (viscoelasticity), and average and local surface chemistry. Besides enabling sensing and separations, the unique dynamic adhesion signatures (skipping, rolling, sliding, arrest) of different bacterial strains and mammalian cells form the basis for their different exposures to antimicrobial functionality, producing selective antimicrobial action, independent of the molecular-scale design. Activities will include synthesis of surface elements and fabrication of surfaces, the experimental study of the dynamic adhesion and viability of bacteria and mammalian cells on these surfaces, the interpretation of data via semiquantitative physico-chemical treatments, and the development of variable-space maps that summarize selectivity, bacterial motion, and viability in a multidimensional materials parameter space. The latter will facilitate rational surface design in diverse applications from implants to clothing.
BROADER IMPACTS: The widespread interest in antimicrobial surfaces is driven by the mounting bacterial resistance to antibiotics. Each year in the US there are 90,000 deaths arising from hospital-acquired infections; of these 50,000 are related to catheter infections. So the effective development of antimicrobial polymeric surfaces could have huge practical implications. This project attacks this problem with innovative thinking and technology. The project offers a multidisciplinary setting in which students will be trained in elements of biology, polymer chemistry, materials science, surface science, adhesion, and biophysics. It is proposed that undergraduate students who have worked on the project will be afforded opportunities for industrial intern experience with relevant companies. Outreach to underrepresented groups will be carried out through participation in the Northeast Alliance for Graduate Education and the Professorate, and K-12 outreach will be carried out in conjunction with the UMass MRSEC.
This program addressed the need for surfaces with the ability to manipulate and ultimately kill bacteria. Broader (Societal) Impact: This need arises from the continued rise in bacterial resistance to antibiotics, the continued increase in hospital infections with a growth in the numbers of deadly infections, and the rise in the use of polymers is medical devices from IV lines and catheters to medical implants. There is a need for surfaces which can readily sense bacteria in public spaces, and a need for materials that come in contact with humans. The latter should be deadly to bacteria but non-toxic. This program addressed this need by developing the science to enable the rational fabrication of new antimicrobial and related surfaces. Technical Significance/ Challenge: Materials have classically been made antimicrobial through the incorporation of antiseptics such as silver, or antibiotics, or newer biomimetic antimicrobial compounds. This approach has the problem that the active compounds are continually released from the material and can accumulate in the local environment and cause undesirable effects. This approach can be both dangerous as wasteful. Intellectual Merit: The Strategy of THIS Approach: This program explored a different approach: the creation of "contact surfaces" which do not release compounds and where the active functionality is permanently attached to the material’s surface. While this approach avoids the waste and toxicity of surfaces that release antibacterial compounds, it faces other challenges. Contact surfaces, if they become fouled (ie they are made dirty and covered with debris,) will never actually come in contact with the bacteria they must ultimately kill. While it might seem simple enough to create surfaces which are resistant to fouling, contact antimicrobial surfaces must be sufficiently sticky to bacteria that when they contact the bacteria, the bacteria are killed. It was therefore a focus of this program to understand how to create surfaces would touch bacteria, attract them, but repel most other molecules and objects. Intellectual Merit Outcomes: The greatest success of this program was creating new surface libraries and demonstrating utility of surfaces which could be selective in their adhesive interactions with biological molecules and cells. While this has been done in the past, prior technology typically exploited antibodies, a particular kind of molecule made and used as part of the immune system. Antibodies are so expensive that it is impractical to use them in the large capacities needed for antimicrobial surfaces. They are also extremely fragile. The current program achieved selective adhesion of biological molecules and cells using polymers and nanoparticles, which are more robust, far less expensive, and when used as demonstrated in this program, non-toxic. The new surfaces placed tiny sticky groups on surfaces at random positions, where the sticky groups were only about 10 nm in size. 10 nanometers is one one hundredth the size of a bacterium and one onethousandth of a blood cell. By localizing the sticky interactions, rather than smearing them out over the entire surface, it was shown that the surfaces could be made to behave like cells themselves, in their interactions with biological objects. In the end, it was shown that these surfaces could have multiple uses: they could be used in pharmaceutical separations to purify proteins (many drugs such as insulin are actually proteins) or they could be used to capture bacteria and not get dirty from proteins that also happened to be present. The next step will be to engineer deadly non-toxic surface chemistry onto these surfaces
