His research involves the application of engineering principles to biological systems. His lab has special expertise in the use of proteins as nanomachines, and in the production of high-value products utilizing enzymes and biological cells.
Industry Expertise (3)
Areas of Expertise (2)
2003-2004 Withrow Teaching Excellence Award (professional)
- Great Lakes Chapter of ISPE, Board of Directors
Expanding biomedical engineering programs could boost state’s life sciences industry
“There’s a lot of interest among prospective students at the graduate and undergraduate levels for study in this area,” Worden said. “We wanted to be able to meet that need and we wanted to be able to leverage scientific fundamental programs that we have here and move that into more applied area through technology development.” [...]
Journal Articles (3)
Krista M Cosert, Rebecca J Steidl, Angelines Castro-Forero, Robert M Worden, Gemma Reguera
The metal-reducing bacterium Geobacter sulfurreducens produces protein nanowires (pili) for fast discharge of respiratory electrons to extracellular electron acceptors such as iron oxides and uranium. Charge transport along the pili requires aromatic residues, which cluster once the peptide subunits (pilins) assemble keeping inter-aromic distances and geometries optimal for multistep hopping. The presence of intramolecular aromatic contacts and the predominantly α-helical conformation of the pilins has been proposed to contribute to charge transport and rectification. To test this, we self-assembled recombinant, thiolated pilins as a monolayer on gold electrodes and demonstrated their conductivity by conductive probe atomic force microscopy. The studies unmasked a crossover from exponential to weak distance dependence of conductivity and shifts in the mechanical properties of the film that are consistent with a transition from interchain tunneling in the upper, aromatic-free regions of the helices to intramolecular hopping via aromatic residues at the amino terminus. Furthermore, the mechanistic stratification effectively “doped” the pilins at the amino terminus, favoring electron flow in the direction opposite to the helix dipole. However, the effect of aromatic dopants on rectification is voltage-dependent and observed only at the low (100 mV) voltages that operate in biological systems. The results thus provide evidence for a peptide environment optimized for electron transfer at biological voltages and in the direction needed for the respiration of external electron acceptors. The implications of these results for the development of hybrid devices that harness the natural abilities of the pilins to bind and reduce metals are discussed.
Ying Liu, Zhen Zhang, Quanxuan Zhang, Gregory L Baker, R Mark Worden
Engineered nanomaterials (ENM) have desirable properties that make them well suited for many commercial applications. However, a limited understanding of how ENM's properties influence their molecular interactions with biomembranes hampers efforts to design ENM that are both safe and effective. This paper describes the use of a tethered bilayer lipid membrane (tBLM) to characterize biomembrane disruption by functionalized silica-core nanoparticles. Electrochemical impedance spectroscopy was used to measure the time trajectory of tBLM resistance following nanoparticle exposure. Statistical analysis of parameters from an exponential resistance decay model was then used to quantify and analyze differences between the impedance profiles of nanoparticles that were unfunctionalized, amine-functionalized, or carboxyl-functionalized. All of the nanoparticles triggered a decrease in membrane resistance, indicating nanoparticle-induced disruption of the tBLM. Hierarchical clustering allowed the potency of nanoparticles for reducing tBLM resistance to be ranked in the order amine > carboxyl ~ bare silica. Dynamic light scattering analysis revealed that tBLM exposure triggered minor coalescence for bare and amine-functionalized silica nanoparticles but not for carboxyl-functionalized silica nanoparticles. These results indicate that the tBLM method can reproducibly characterize ENM-induced biomembrane disruption and can distinguish the BLM-disruption patterns of nanoparticles that are identical except for their surface functional groups. The method provides insight into mechanisms of molecular interaction involving biomembranes and is suitable for miniaturization and automation for high-throughput applications to help assess the health risk of nanomaterial exposure or identify ENM having a desired mode of interaction with biomembranes.
Alexander Negoda, Kwang-Jin Kim, Edward D Crandall, Robert M Worden
A diverse range of molecular interactions can occur between engineered nanomaterials (ENM) and biomembranes, some of which could lead to toxic outcomes following human exposure to ENM. In this study, we adapted electrophysiology methods to investigate the ability of 20 nm polystyrene nanoparticles (PNP) to induce pores in model bilayer lipid membranes (BLM) that mimic biomembranes. PNP charge was varied using PNP decorated with either positive (amidine) groups or negative (carboxyl) groups, and BLM charge was varied using dioleoyl phospholipids having cationic (ethylphosphocholine), zwitterionic (phosphocholine), or anionic (phosphatidic acid) headgroups. Both positive and negative PNP induced BLM pores for all lipid compositions studied, as evidenced by current spikes and integral conductance. Stable PNP-induced pores exhibited ion selectivity, with the highest selectivity for K+ (PK/PCl ~ 8.3) observed when both the PNP and lipids were negatively charged, and the highest selectivity for Cl− (PK/PCl ~ 0.2) observed when both the PNP and lipids were positively charged. This trend is consistent with the finding that selectivity for an ion in channel proteins is imparted by oppositely charged functional groups within the channel's filter region. The PK/PCl value was unaffected by the voltage-ramp method, the pore conductance, or the side of the BLM to which the PNP were applied. These results demonstrate for the first time that PNP can induce ion-selective pores in BLM, and that the degree of ion selectivity is influenced synergistically by the charges of both the lipid headgroups and functional groups on the PNP.