Investigations of the Adhesive Properties of Phragmatopoma californica Eggs Annie Chiu Hopkins Marine Stations, Pacific Grove, CA, 93950 Spring 1993, 17 Investigations of the Adhesive Properties of Phragmatopoma californica Eggs Annie Chiu Hopkins Marine Station, Pacific Grove, CA, 93950 Spring 1993, 175H Abstract Phragmatopoma californica is a marine annelid that sheds sticky eggs. The adhesion of the eggs was found to be dependent on trace levels of calcium. Transglutaminase inhibitors dansylcadaverine and putrescine prevented or lowered stickiness, indicating the involvement of tranglutaminase cross-linking in the adhesion process. Other substrates that prevented stickiness were protease and ethylenediamine. The egg surface adhered to a polylysine coat, indicating a negatively-charged membrane. Adhesion does not appear to follow the model system of Mytilus edulis, so P. californica may present a new system of adhesion in water. Introduction Phragmatopoma californica is an intertidal polychaete that sheds eggs that adhere to many surfaces. Previous investigations of the species have focused on the metamorphosis (Dales, 1952; Eckelbarger and Chia, 1976; Eckelbarger, 1977), reef-building (Waite, et al, 1992), and settling patterns (Barry, 1989; Eckelbarger, 1976). No mention is made in past literature describing or studying the adhesive properties of the eggs, with the exception of a brief description given by Strathmann (1987) for the family Sabellariidae. Phragmatopoma originally included two species, P. lapidosa and P. californica. The two species are now considered a single species, called P. lapidosa californica (Barry, 1989), or simply P. californica. The species is reef-dwelling, living in colonies of mixed sexes (Barry, 1989). Colonies continually increase in size when larvae settle on existing adult tubes (Eckelbarger, 1976). P. californica build their sand tubes by cementing grains of sand with organic mortar containing high levels of 3,4-dihydroxyphenyl-L-alanine (DOPA) (Waite, 1992). The presence of DOPA in the mortar suggests use of the mussel adhesion system as a model for the stickiness of the eggs. The mussel Mytilus edulis uses byssus threads containing DOPA for adhesion (Waite, 1985). The byssus threads contain scleroproteins which increase the mechanical strength of the threads. These scleroproteins are stabilized by protein cross-linking. Cross-linking enzymes which may be involved include transglutaminase, lysyl oxidase, and peroxidase (Waite, 1983). P. californica was hypothesized to follow the M. edulis adhesion system for the stickiness of its eggs. Enzyme inhibitors for the above enzymes were tested, and results suggested the involvement of transglutaminase in egg adhesion. However, other evidence suggests that the adhesive eggs do not directly conform to the mussel model system. Materials and Methods P. californica colonies were collected from the intertidal zone at Boat Works Beach, Hopkins Marine Station, throughout the time of the study. Eight colonies were used in the study, with successful spawning in all but one of the colonies. Worm tubes were isolated from the colony fragment using forceps, then transferred to the desired test solution for spawning. Worms spawned spontaneously when the tube was broken. In a few cases, worms began shedding when stressed, before the tube was fully isolated. In these cases, the whole colony fragment was transferred to the different conditions. Eggs from each worm were used for multiple tests by transferring the shedding worm to bowls containing different solutions. Spawning and handling of the worms was carried out as described by Costello, et al (1957) for the related species Sabellaria vulgaris. The worms were maintained in a tank with flowing seawater, and colonies were replaced every 2-3 weeks. Egg adhesiveness was measured using a manometer to monitor water pressure required to free the eggs from a glass surface (30-ml glass bowl; diameter S cm, height 3.5 cm). An elevated bottle with a bottom spout served as the water source. The bottle was connected to tubing leading to a manometer (1-ml pipette) and pipette tip. A clamp to control water pressure was placed on the tubing between the water source and the manometer. UV-treated, filtered seawater (FSW) was used to measure water pressure in all solutions. The experiments were conducted using two methods. The first required spawing directly into test solutions by placing the shedding worm into the test solution. The test solutions were FSW, calcium-free seawater (OCaSW), OCaSW with ethylenediaminetetraacetic acid (EDTA; 5 mM), FSW with protease (0.1%) or borate (10 mM), and FSW with a polylysine surface coat (five microliters of polylysine in 450 microliters of distilled water applied to the bottom of a glass bowl, then blotted off and allowed to dry). The second method involved spawning into OCaSW-O.02 M glycylglycine (pH 8) with EDTA as a chelator, then slowly decanting off the OCaSW, and pouring on a different solution. Enzyme inhibitors for transglutaminase, peroxidase, trypsin, and lysyl oxidase were tested using this method. See Table 1. Adhesiveness was also tested on different surfaces, both synthetic and natural. Eggs were shed directly onto the surfaces, allowed to settle for several minutes, then tested for their stickiness to each surface. These tests were performed in a petri dish rather than a glass bowl, so the results do not directly correlate to the tests above. Also, fewer trials were performed on each surface, resulting in more error in the measurements. The controls for adhesion were eggs spawned in FSW for stickiness, and demembranated eggs for unstickiness. Demembranation was carried out using a 1:1 solution of 0.25 M sodium citrate and 1 M sucrose (pH adjusted to 5-6 with hydrochloric acid) according to Winesdorfer (1967). The majority of the experiments used unfertilized eggs, although unintended fertilization was observed in some cases, and may have slightly affected results. Fertilized eggs were tested for stickiness during various stages of early development. No readily visible indications of fertilization were apparent prior to cleavage, so testing prior to first cleavage was not possible. Results While spawning was successful in early April, many more eggs were obtained per worm in late May, indicating that the natural season for spawning begins in late spring (as also stated by Abbott, et al, 1980). Eggs were shed from each body segment, and emerged in single-cell columns. The eggs did not appear to stick well to one another, however, as light agitation disrupted the cell column. Upon reaching a surface such as glass, the eggs seemed firmly adhered at contact, although the actual time required to cause stickiness is unknown. The effects of altering proteins and carbohydrates were measured by spawning into protease and borate to break down surface proteins and oxidize surface carbohydrates, respectively. The charge of the egg surface was also measured using a positively-charged polylysine coat on the glass. Results (Fig. 1) showed reduction of adhesion by protease, and increase by polylysine. Borate results were inconclusive. Measurements of adhesion after fertilization showed a slight increase in stickiness following the early cleavages (Fig. 2). The envelope was successfully removed after fertilization using the sodium citrate/sucrose solution, and demembranated embryos were unsticky. This is contrary to Strathmann (1987), which suggests that demembranated eggs and embryos are sticky. Observed demembranation of unfertilized eggs also eliminated stickiness, so this condition was used as a control for the stickiness (Fig. 3). Spawning into various conditions of calcium resulted in different levels of adhesion (Fig. 4). Calcium-free seawater lowered stickiness only slightly, but addition of EDTA as a chelator substantially lowered the adhesion. Addition of CaCl crystals and transfer to FSW restored stickiness. Enzymes involved in scleroprotein stabilization in the M. edulis model were tested using several inhibitors (Table 1.) Dansylcadaverine (DC), putrescine (PUT), and ethylenediamine (EDA) were the only inhibitors that showed a consistent prevention or decrease of stickiness (Fig. 5). Only sulfanilate (SUL) could be considered uninhibiting to the adhesion process, while the other inhibitors remain inconclusive. DC was the most effective inhibitor of stickiness, so a concentration dilution series was tested from 10-4 to 10-8 M (Fig. 6). Effective inhibition was observed up to O.1 uM. A survey of stickiness was conducted on different surfaces, suggesting a variable adhesion to different surfaces (Fig. 7). Only extreme values were consistent, showing Iridea, Macrocystis, and plastic to be very low in adhesiveness, while glass was very high. No conclusions could be made about the other surfaces, as the standard deviations were very high. Discussion The results of this study indicate that the membrane of P. californica eggs has properties of other egg outer coats. The strong adhesion to a positively-charged polylysine coat indicates a negative charge on the egg, a common feature in other species, including Stronglyocentrotus purpuratus. Calcium appears to effect adhesion, even at very low levels. The elimination of calcium and trace metals with a chelator was necessary to lower stickiness substantially. Calcium may be acting on the egg either directly, as a cofactor for an enzyme or as a secondary messenger. Direct action may involve a Ca2--dependent system such as that in cell-cell interactions for keratinocytes (Alberts, et al., 1989). However, the need to remove all traces of Ca2* (or trace metals) suggests that Ca2+ may be acting as a cofactor or secondary messenger. Decreased adhesion in observed solutions of DC and PUT suggest that the cross- linking enzyme transglutaminase (TGase) may be involved. Although EDA was consistently low, BAPN results were inconclusive, so the presence of lysyl oxidase is not conclusive. EDA may have affected the cell in a manner other than a lysyl oxidase inhibitor. For example, EDA is a weak chelator and may have removed a necessary metal other than calcium. Furthermore, EDA may serve as an inhibitor for TGase, acting as a primary amine competitive inhibitor (Lorand, 1979). DC was the most effective inhibitor of stickiness, and is known as the highest affinity inhibitor for TGase (Lorand, 1979). It was a potent inhibitor at very low concentrations, up to 10-7 M (O.1 uM), arguing against the possibility that DC was directly affecting the egg rather than acting on the enzyme. Although the results for GEE are inconclusive, the consistent inhibition of stickiness by DC and PUT suggests that TGase is involved in increasing egg adhesion. The calcium requirement for adhesion further reinforces the presence of TGase in triggering egg adhesion, since TGase is calcium dependent. The ability to inhibit stickiness could increase the usefulness of P. californica as a model for annelid development. Controlling egg stickiness, by spawning in O.1 uM DC, would permit experimental manipulations, such as treatments in different solutions without centrifugation that could be damaging to the eggs. The role of TGase in causing egg adhesion is unknown. TGase acts by cross- linking lysine and glutamine residues in peptide bonds in a transamidation reaction (Stryer, 1988). The most studied TGase activity is in the cross-linking of fibrin for blood clotting TGase activity has also been dicovered in fertilization envelope assembly in Stronglyocentrotus purpuratus eggs (Battaglia and Shapiro, 1988), endocytosis of yolk protein in Xenopus laevis eggs (Tucciarone and Lanclos, 1981), and exocytosis of transferrin receptors in rat reticulocytes (Grasso, et al, 1990). Several hypotheses for the role of TGase in P. californica egg adhesion are presented here, but they are merely speculative. One possibility is a conformational change imposed on surface proteins. Proteins may have regions of stickiness that initially are not exposed. TGase action may alter the proteins so that the sticky regions are available for adhesion. Another hypothesis is that sticky proteins may be present in somewhat sparse distribution around the cell, but upon contact with a surface, the proteins are cross-linked so they are concentrated at the region of contact. This would result in increased order and concentration of sticky proteins at the area of contact. Alternately, Ca24 and TGase may be involved in the exocytosis of vacuoles containing a sticky substance from within the egg, perhaps upon contact with seawater. Results of adhesion to different surfaces suggests that only the extreme results are valid while the others are inconclusive. The results may be highly inconclusive due to the subjectivity of the test. Water pressure was applied until the majority of the eggs were freed from the surface, but the definition of majority was subjective for each trial, especially since the eggs were distributed differently on each surface. Furthermore, the eggs had a natural variation of stickiness. The variation may not have been evenly distributed such that a certain area of eggs may have had extremely sticky or unsticky eggs. These problems had no controls for consistency, so they may have added to the error in measurements. Because of the subjectivity of the tests, slight differences in water pressure are not significant. The variable adhesion to different surfaces poses the question of how the eggs are attched to the surface. Perhaps two factors, the charge of the egg and the action of TGase determine the adhesion to any surface. This hypothesis, however, would require that the less adhesive surfaces are either more negatively charged, or somehow prevent the action of TGase. The factors affecting stickiness should be investigated further. The significance of the sticky eggs in nature is also unknown. However, the water pressure necessary to free the eggs from any tested surface appears to be far less than the pressure of the waves in the intertidal region. Perhaps the eggs can resist surge or swells, so they can settle and adhere to the ocean bottom once they are carried past the surf zone. Adhesion in water is a phenomena with both biological and industrial significance. Biologically, the significance of egg adhesion may be to increase the fertilization rate of the eggs (by reducing dilution rate of eggs), or reduce predation by plankton-consuming animals in the early stages after fertilization (since the eggs would be on the ocean floor rather than free-floating). P. californica fertilization appears to be very successful, as larvae are abundant in plankton (Eckelbarger, 1976). This reproductive success may be attributed in part to the adhesion of the eggs. Industially, the adhesion of P. californica eggs may serve as a model for making synthetic adhesives for use in marine environments. Adhesion in water has been difficult to achieve artificially, but adhesives have important industrial value in the building of bridges and other water structures. The relation between the M. edulis byssus threads and P. californica adhesion systems is still unknown. P. californica egg adhesion does seem to use an enzyme, TGase, that is involved in scleroprotein stability. However, some evidence suggests that the two systems are not similar. Demembranation was possible in a solution of sodium citrate and sucrose, whereas the proteins in mussel are insoluble. Spawning in a protease solution also decreased egg stickiness, while mussel proteins are resistant to protease. Therefore, and P. californica eggs do not appear to conform directly to the mussel model system. The P. californica adhesive eggs pose many interesting questions that require further experimentation. Literature Cited Abbott, Donald P., Robert H. Morris, and Eugene C. Haderlie. 1990. Intertidal invertebrates of California. Stanford: Stanford University Press. Alberts, Bruce, et al. 1989. Molecular Biology of The Cell (Second Edition). New York: Garland Publishing, Inc. p. 828. Barry, James P. 1989. Reproductive response of a marine annelid to winter storms: an analog to fire adaptation in plants? Mar. Ecol. Prog. Ser. 54:99-107. Battaglia, David E. and Bennett M. Shapiro. 1988. Hierarchies of Protein Cross-linking in the Extracellular Matrix: Involvement of an Egg Surface Transglutaminase in Early Stages of Fertilization Envelope Assembly. J. Cell Biol. 107(6):2447-2454. Costello, D.P. 1957. Methods for Obtaining and Handling Marine Eggs and Embryos. Lancaster: Lancaster Press, Inc. pp. 91-97. Dales, R. Phillips. 1952. The Development and Structure of the Anterior Region of the Body in the Sabellariidae, with Special reference to Phragmatopoma californica. Quarterly J. Microscopical Sci. 93(4):435-452. Eckelbarger, Kevin J. 1976. Larval development and population aspects of the reef- building polychaete Phragmatopoma lapidosa from the east coast of Florida. Bull. Mar. Sci. 26(2):117-132. Eckelbarger, Kevin J. and Fu-Shiang Chia. 1976. Scanning electron microscope observations of the larval development of the reef-building polychaete Phragmatopoma lapidosa. Can. J. Zool. 54:2082-2088. Eckelbarger, Kevin. J. 1977. Larval development of Sabellaria floridensis from Florida and Phragmatopoma califonica from Southern California (Polychaeta: Sabellariidae), with a key to the Sabellariid larvae of Florida and a review of development in the family. Bull. Mar. Sci. 27(2):241-255. Grasso, J.A., et al. 1990. Calmodulin dependence of transferrin receptor recycling in rat reticulosytes. Biochem. J. 266(1):261-272. Lorand, L., et al. 1979. Specificity of Guinea Pig Liver Transglutaminase for Amine Substrates. Biochemistry. 18(9):1756-1765. Strathmann, Megumi, F. 1987. Reproduction and Development of Marine Invertibrates of the Northern Pacific Coast. Seattle: University of Washington Press. pp. 166-169. Stryer, Lubert. 1988. Biochemistry, Third Edition. New York: W.H. Freeman and Company. p. 250. Tucciarone, Linda M. and Kenneth D. Lanclos. 1981. Evidence for the involvement of transglutaminase in the uptake of vitellogenin by Xenopus laevis oocytes. Biochem. Biophys. Res. Comm. 99(1):221-227). Waite, J.H. 1983. Quinone-Tanned Scleroproteins. In The Mollusca (Karl M. Wilbur) New York: Academic Press. pp. 467-504. Waite, J.H., Timothy J. Housley, and Marvin L. Tanzer. 1985. Peptide Repeats in a Mussel Glue Protein: Theme and Variations. Biochemistry. 24(19):5010-5014. Waite, J.H., Rebecca A. Jensen, and Daniel E. Morse. 1992. Cement Precursor Proteins of the Reef-Building Polychaete Phragmatopoma californica (Fewkes). Biochemistry. 31(25):5733-5738. Winesdorfer, John E. 1967. Marine Annelids: Sabellaria. In Methods in developmental biology (Fred H. Wilt and Norman K. Wessels). New York: Thomas Y. Crowell. pp. 157-162. 10 Table 1. Enzyme Inhibitors Transglutaminase Peroxidase Trypsin (control) Lysyl Oxidase Glycine Ethyl Ester (10 mM) Dansylcadaverine (1 mM) Putrescine (1 mM) Sulfanilate (0.2 mM) Soybean Trypsin Inhibitor (1 mg/ml) Bovine Serum Albumin (1 mg/ml) Ethylenediamine (0.1 mM) B-aminopropionitrile (0.25 mg/ml) Figure Legends Fig. 1 Spawing directly into different solutions to test the effects of altering surface proteins and carbohydrates, and to test charge of surface. OCa-OCaSW w/EDTA; FSW-filtered seawater; PRO-protease; BOR-borate; PLY-polylysine coat. Clear region is standard deviation, grey is mean value. Y-axis is relative stickiness. Fig. 2 Adhesion before and after fertilization (at 2-4 cell and 32-64 cell stages). All were spawned directly into normal seawater. Fig. 3 Membranated and demembranated eggs, in normal seawater. OCaSW with EDTA is present for comparison. Demembranated eggs are the control for unstickiness. Fig. 4. Varying conditions of calcium. FSW-filtered seawater; OCa-calcium-free seawater without chelator; EDTA-OCaSW with EDTA as a chelator; CaCl2-addition of CaCla crystals to OCaSW w/EDTA; »FSW-transfer from OCaSW w/EDTA to filtered seawater. Fig. 5 Spawning into OCaSW w/EDTA then transferring to different enzyme inhibitors. GEE-glycine ethyl ester; DC-dansylcadaverine; PUT-putrescine; EDA-ethylenediamine BAPN-B-aminopropionitrile; SUL-sulfanilate; STI-soybean trypsin inhibitor; BSA=bovine serum albumin. Lowered stickiness (considering standard deviations) was apparent only for DC, PUT, and EDA. Fig. 6 Logarithmic concentration dilution curve for dansylcadaverine. Inhibition of adhesion is apparent until 107 M. Fig. 7 Spawning onto different surfaces. Surfaces (from left to right) are: Iridaea, Macrocystis, Gigartina canaliculata, Cystoseira, Gigartina leptorhynchos, rough rock, sand tube, keyhole limpet shell, smooth rock, plastic, and glass. 12 30 FS oca Fig. 1 PR BO PLY 30 Fig. 2 SW unfert SW fert (2-4) SW fert (32-64) 14 whole dememb. OCa W/EDTA Caciz EDT calcium conditions FSV Fig. 5 A OCa FSWG DC PUT EDA BAPN SUL STI BSA a 11• 10 - Fig 4aaka- 7 -6 -5 -4 -3 -9 -8 loglDCI (M) a. . Fig. 7