Proteobionics: Biomimetics in Proteomics Andrei P. Sommer*,† and Eleonora Gheorghiu‡ Central Institute of Biomedical Engineering, University of Ulm, 89081 Ulm, Germany and National Institute for Pharmaceutical-Chemical R&D, 031299 Bucharest, Romania Received November 2, 2005
Proteomics was established 10 years ago by the analysis of microbial genomes via their protein complement or proteome. Bionics is an ancient art, which converts structures optimized by nature into advanced technical products. Previously, we analyzed survival modalities in nanobacteria and converted the interplay between survival-oriented protein functions and nanoscale mineral shells into models for advanced drug delivery. Exploiting protein functions observed in nature to design biomedical products and therapies could be named proteobionics. Here, we present examples for this new branch of nanoproteomics. Keywords: proteobionics • biomimetics • drug delivery • nanovesicles • nanoparticles • HIV
Introduction Scientific discoveries can be stimulated by a $1000 invitation: think small (1959),1 creation of a descriptive term: biomimetics (1969),2 proteomics (1995),3 or a prediction: postproteome era.4 New developments in proteomics, in particular in the global field of interaction proteomics, have standardized nano thinking in proteomics. We introduced biomimetics into the field of proteomics on the basis of nanobacteria (NB)5 and the primordial proteins (PP) synthesized by them.6 Analysis of the functions and properties of the PP turned out to be extremely fruitful and led to an extensive catalog of protein modifications, as response patterns to environmental changes,7 which provided a synoptic view of possible evolutionary implications of early proteins.8 Proteomic technologies have already proven useful to study the response of bacterial cells to conditions of environmental stress.9 Here, we continue to explore the response of NB to environmental changes, and extend our model in the light of the recent discovery of NB,6 and proteins10, in the atmosphere. We are particularly interested in cooperative responses in ensembles of proteins, triggered by external stimuli. In our earlier work, we investigated the functions of PP in NB by analyzing their modifications in response to transits between various environments, and identified a synergistic interplay between two intrinsic characteristics of NB: the fluid PP-based slime envelope, and the protective mineral shell.11 Biosystems with exceptional functions optimized by nature are today in the focus of biomimetics. In NB, the optimization comprises principally a balanced interaction between the elements surface sealing, bioadhesivity, slime fluidity and overall size. The apatite shell and the PP film equip NB with an extensively variable bioadhesive capacity. Laboratory experi* To whom correspondence should be addressed. E-mail: samoan@ gmx.net. † Central Institute of Biomedical Engineering, University of Ulm. ‡ National Institute for Pharmaceutical-Chemical R&D. 10.1021/pr050370s CCC: $33.50
2006 American Chemical Society
ments provided convincing evidence that NB, which have passed the bladder of animalssprobably a slime-depleting processswere capable of crossing the cell membrane and reaching the nuclear membrane of 3T6 cells.12 Poration of cellular membranes is possibly facilitated by the size of the apatite nanovesicles (60-300 nm). Engulfment is another possible variant for entry. Transport across membranes is believed to be further facilitated by the apatite itselfsa material similar to the mineral constituent of bone. Indeed, slime-free NB could be virtually invisible to the immune defense. Here, we study details of three distinct processes, thought to be relevant in the transfection of eukaryotic cells with nucleic acids, discussed by us in the lymphocyte model.8 The first is transport of NB (bare or masked with PP) across the cell membrane, the second diffusion through the cytoplasm, and the third attachment to the nuclear membrane. Without PP, NB may cross this membrane too; they may even use the nuclear pores as portals of entry into the nucleus.13
Proteobionics on the NanoscalesLearning from Nature NB infections have been suspected to contribute to an increase in the genetic diversity of the HIV-virus by acting as natural transfection vectors in HIV-infected CD-4 cells.14 The predominant mode of transfection in our model is across the nuclear membrane, with calcium phosphate stored in the slime envelope as mediator.8 Prior to contacting the nuclear membrane, invading NB must pass the cell membrane and the cytoplasm. The entry of NB into eukaryotic cells is documented in the literature.15 Smaller NB, with diameters
